A trial of metaproterenol by metered‐dose inhaler and two spacers in preschool asthmatics

König, Peter; Gayer, Debra; Kantak, Anand; Kreutz, Cynthia; Douglass, Barbara; Hordvik, Nancy L.

doi:10.1002/ppul.1950050412

Cited by 20 publications

(5 citation statements)

References 12 publications

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“…In placebo-controlled studies, FOT was useful to document therapeutic response to bronchodilators, such as theophylline, terbutaline, or ipratropium bromide (197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207). The criteria (and cutoff values) for diagnosis of meaningful reversibility postbronchodilation are reported in Table 9.…”

Section: Asthmamentioning

confidence: 99%

An Official American Thoracic Society/European Respiratory Society Statement: Pulmonary Function Testing in Preschool Children

Beydon

Davis

Lombardi

et al. 2007

Am J Respir Crit Care Med

1,063

980

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on behalf of the American Thoracic Society/ European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing This official statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) was approved by the ATS Board of Directors, September 2006, and the ERS Executive Committee, December 2006 6. Further multidisciplinary work is required to investigate the best combination of tests (e.g., structure, function, inflammation, atopy) and challenges (e.g., pharmaceutical vs. physical) to investigate specific clinical entities during early childhood.

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Section: Asthmamentioning

confidence: 99%

An Official American Thoracic Society/European Respiratory Society Statement: Pulmonary Function Testing in Preschool Children

Beydon

Davis

Lombardi

et al. 2007

Am J Respir Crit Care Med

1,063

980

View full text Add to dashboard Cite

show abstract

“…Regular injections are a particular hardship for children, and the substitution of inhaled capreomycin in that population seems especially desirable and feasible. Studies done with asthmatic children in Europe, the Americas, and Asia have shown the feasibility and acceptability of the use of a metered dose and a dry powder inhaler device of asthma drugs by children (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Phase I, Single-Dose, Dose-Escalating Study of Inhaled Dry Powder Capreomycin: a New Approach to Therapy of Drug-Resistant Tuberculosis

Dharmadhikari

Kabadi²,

Gerety³

et al. 2013

Antimicrob Agents Chemother

115

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dMultidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and when given as intramuscular injections, dosing can be painful. Advances in particulate drug delivery have led to the formulation of capreomycin as the first antituberculosis drug available as a microparticle dry powder for inhalation and clinical study. Delivery by aerosol may result in successful treatment with lower doses. Here we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability in healthy subjects and measuring pharmacokinetic (PK) parameters. Twenty healthy adults (n ‫؍‬ 5 per group) were recruited to self-administer a single dose of inhaled dry powder capreomycin (25-mg, 75-mg, 150-mg, or 300-mg nominal dose) using a simple, handheld delivery device. Inhalations were well tolerated by all subjects. The most common adverse event was mild to moderate transient cough, in five subjects. There were no changes in lung function, audiometry, or laboratory parameters. Capreomycin was rapidly absorbed after inhalation. Systemic concentrations were detected in each dose group within 20 min. Peak and mean plasma concentrations of capreomycin were dose proportional. Serum concentrations exceeded 2 g/ml (MIC for Mycobacterium tuberculosis) following the highest dose; the half-life (t 1/2 ) was 4.8 ؎ 1.0 h. A novel inhaled microparticle dry powder formulation of capreomycin was well tolerated. A single 300-mg dose rapidly achieved serum drug concentrations above the MIC for Mycobacterium tuberculosis, suggesting the potential of inhaled therapy as part of an MDR-TB treatment regimen. M ultidrug-resistant tuberculosis (MDR-TB) is difficult to treat and readily spread and threatens global tuberculosis control, especially where HIV coinfection is common. According to the WHO, an estimated 440,000 new cases of MDR-TB occur each year (1, 2), but only a small fraction are receiving qualityassured treatment (1). In most public health treatment programs, 18 to 24 months of therapy with four or more second-line drugs are required. Second-line drugs are less efficacious, more toxic, and associated with treatment success rates of only 40 to 80% (1, 3-6). According to current WHO MDR-TB treatment guidelines, at least one injectable antibiotic (kanamycin, amikacin, or capreomycin) is an essential part of the 6-month intensive phase of treatment. These 3-to 7-times-per-week injections are painful for patients, especially for children and those with little muscle mass. Injections require skilled health care staff and place them at risk of needle stick injuries and infections (3). Treatment with injectable drugs is associated with systemic toxicity, including nephrotoxicity, which is typically mild and reversible, and ototoxicity, which can be significant and irreversible. Dosing must also be adjusted in individuals with preexisting renal...

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“…An average decrease of 12% in Rrs5 was observed in the healthy children; to exceed the 95% confidence interval for bronchodilator response in healthy children, a cut-off value of a 41% decrease in Rrs5 should be used to support the diagnosis of asthma in reversibility testing [44]. In young children, FOT has been shown to provide a useful and objective method to assess airway responses to bronchodilator drugs, such as metaproterenol, ipratropium bromide or salbutamol versus placebo [87][88][89][90], and to characterise dose/response curves [88,91]. For example, the bronchodilating effect of nebulised oxitropium bromide (750 and 1500 mg) in preschool asthmatic children was shown to last for up to 4 h postinhalation, whereas no additive bronchodilation by fenoterol could be shown [92] .…”

Section: Reversibilitymentioning

confidence: 99%

The forced oscillation technique in clinical practice: methodology, recommendations and future developments

Oostveen¹,

MacLeod²,

Lorino³

et al. 2003

European Respiratory Journal

1,083

1,120

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The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory mechanics. FOT employs small-amplitude pressure oscillations superimposed on the normal breathing and therefore has the advantage over conventional lung function techniques that it does not require the performance of respiratory manoeuvres.The present European Respiratory Society Task Force Report describes the basic principle of the technique and gives guidelines for the application and interpretation of FOT as a routine lung function test in the clinical setting, for both adult and paediatric populations.FOT data, especially those measured at the lower frequencies, are sensitive to airway obstruction, but do not discriminate between obstructive and restrictive lung disorders. There is no consensus regarding the sensitivity of FOT for bronchodilation testing in adults. Values of respiratory resistance have proved sensitive to bronchodilation in children, although the reported cutoff levels remain to be confirmed in future studies.Forced oscillation technique is a reliable method in the assessment of bronchial hyperresponsiveness in adults and children. Moreover, in contrast with spirometry where a deep inspiration is needed, forced oscillation technique does not modify the airway smooth muscle tone. Forced oscillation technique has been shown to be as sensitive as spirometry in detecting impairments of lung function due to smoking or exposure to occupational hazards. Together with the minimal requirement for the subject9s cooperation, this makes forced oscillation technique an ideal lung function test for epidemiological and field studies. Novel applications of forced oscillation technique in the clinical setting include the monitoring of respiratory mechanics during mechanical ventilation and sleep.

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A trial of metaproterenol by metered‐dose inhaler and two spacers in preschool asthmatics

Cited by 20 publications

References 12 publications

An Official American Thoracic Society/European Respiratory Society Statement: Pulmonary Function Testing in Preschool Children

An Official American Thoracic Society/European Respiratory Society Statement: Pulmonary Function Testing in Preschool Children

Phase I, Single-Dose, Dose-Escalating Study of Inhaled Dry Powder Capreomycin: a New Approach to Therapy of Drug-Resistant Tuberculosis

The forced oscillation technique in clinical practice: methodology, recommendations and future developments

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