Ten patients with chronic bronchitis, whose FEV1.0 varied between 0.48 and 3.00 1, inhaled uniform 5-micronm particles tagged with technetium-99 in tidal volumes (VT) varying between 750 and 1830 ml. Their chests were scanned after inhalation to ascertain depth of deposition of the particles, and clearance from the lungs was monitored for 5 hr by serial whole-lung gamma counting. A significant inverse relationship (P less than .05) was found between depth of deposition after inhalation (D), measured horizontally across the lung as percentage per inch, and rate of clearance of the particles (5-hr retention [%] = 100- % cleared at 5 hr=69.12-3.02D). This confirmed previous findings. The depth of deposition depended directly on the FEV1.0 and VT (5-hr retention [%] = 0.026VT + 12.67FEV1.0-4.13); this resulted in a 14%-75% range for 5-hr retention. Regression slopes for VT and FEV1.0 were independently significant (P less than .05). The findings suggest that, as commonly administered at present, the therapeutic efficiency of most drugs given be aerosol will be reduced in proportion to the degree of airway obstruction as measured by the FEV1.0. The efficiency can be enhanced by increasing the depth of inspiration of the aerosol.

Aerosols↗

PubMedDate not supplied

Low incidence of paradoxical bronchoconstriction with bronchodilator drugs administered by Respimat Soft Mist inhaler: results of phase II single-dose crossover studies.

BACKGROUND AND OBJECTIVES: Respimat Soft Mist Inhaler (SMI) is an innovative device that offers improved lung deposition and is an environmentally friendly alternative to conventional, chlorofluorocarbon-containing metered-dose inhalers (CFC-MDIs). The aqueous formulations of bronchodilator drugs administered from Respimat SMI contain low concentrations of ethylene diamine tetra-acetic acid (EDTA), a stabilising agent, and benzalkonium chloride (BAC), an antibacterial agent, both of which have been associated with bronchoconstriction when administered via nebulisers. The aim of this retrospective analysis was to compare the incidence of paradoxical bronchoconstriction with bronchodilator drugs administered via Respimat SMI or a CFC-MDI in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: Nine randomised, active- and/or placebo-controlled, double-blind, crossover studies, in which asthmatic and COPD patients (n = 444 and n = 216, respectively) received a beta(2)-agonist and/or anticholinergic or placebo via Respimat SMI or CFC-MDI, were included in the analysis. The incidence of conditions indicative of paradoxical bronchoconstriction were collated and divided into four categories: (1) 'bronchospasm'; (2) two or more of the following events: 'other respiratory adverse events', 'rescue medication use' or 'asymptomatic drop in forced expiratory volume in one second' (FEV(1)); (3) either 'rescue medication use' or 'other respiratory adverse event'; (4) 'asymptomatic drop in FEV(1)'. RESULTS: The incidence of adverse events indicative of paradoxical bronchoconstriction was low in those patients using the Respimat SMI device, and similar to that seen in the CFC-MDI group. In addition, the incidence of adverse events indicative of paradoxical bronchoconstriction observed in the Respimat SMI group was similar for BAC + EDTA and BAC-only drug formulations. CONCLUSIONS: These studies demonstrate that, due to the extremely low absolute amounts of BAC and EDTA delivered to the lungs by the device, Respimat SMI is safe with regard to paradoxical bronchoconstriction in patients with asthma or COPD.

Adrenergic beta-Agonists↗

PubMedDate not supplied

[The modulator effect of bradykinin with respect to tracheobronchial clearance in healthy subjects].

Bradykinin (Bk), a vasoactive nonapeptide which has been proposed as mediator in the pathogenesis of bronchial asthma, is a potent secretagogue in canine airways and in human nasal mucosa in vivo. A study was carried out in order to evaluate the effect of inhaled Bk on tracheobronchial clearance (TBC), measured by a radioaerosol technique in 10 healthy volunteers. Subjects inhaled Bk (8 mg/mL) or vehicle placebo on two occasions, at least 2 weeks apart, in a double blind and randomized fashion 30 min after radioaerosol inhalation. TBC, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 hours (AUC 0-6h), was enhanced in 9 of 10 subjects following inhaled Bk when compared to placebo. The mean values for AUC 0-6h were significantly reduced from 132%.h to 92%.h (p < 0.001) with placebo and Bk respectively. We conclude that Bk has a marked effect on tracheobronchial clearance in normal human airways.

Adult↗

PubMedDate not supplied

Mucus clearance from peripheral and central airways of asymptomatic cigarette smokers.

Insoluble radioaerosol particles have been used to monitor mucus clearance from peripheral, intermediate and inner lung zones. Nine asymptomatic cigarette smokers and nine healthy non-smokers who closely matched them for age, height and lung function were each tested twice under differing radioaerosol inhalation conditions ('high' and 'low' flow rate inhalation), so that clearance differences between smokers and non-smokers should not be masked by apparent clearance differences merely resulting from differing aerosol deposition patterns. Peripheral zone clearance in the smokers was closely similar to that in the non-smokers and was affected very little by changing from 'low' to 'high' flow rate inhalation. Inner zone clearance (calculated by a method which makes allowance for material cleared into the inner zone from more distal airways) was significantly slower in smokers than in nonsmokers for both inhalation conditions. In fact, inner zone clearance in the smokers after 'high' flow inhalation (favouring central aerosol deposition) was slower (p congruent to 0.05) than in the non-smokers after 'low' inhalation (favouring relatively peripheral deposition).

Adult↗

PubMedDate not supplied

Deposition and clearance of inhaled particles.

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Adrenal Cortex Hormones↗

PubMedDate not supplied

Peripheral airways mucus clearance in stable asthma is improved by oral corticosteroid therapy.

Inhaled 99mTc-labelled particles have been used to assess mucus clearance from peripheral, intermediate and inner lung zones of 12 patients with stable asthma. The method of analysis relies on a ventilation image with 81mKr to estimate the distribution of radioaerosol alveolar deposition so that clearance from each zone can be related just to particles deposited in the ciliated conducting airways. In calculating clearance from intermediate and inner lung zones, allowance is made for particles transported into these zones from more distal regions of the lung. Peripheral zone clearance in the asthmatic subjects improved significantly (p less than 0.01) after four weeks of corticosteroid treatment (two weeks on 15 mg prednisolone orally each day, plus two weeks on 30 mg). No significant change occurred in clearance from the inner zone when all patients were considered together. However, the six patients who prior to treatment coughed relatively infrequently did show a significant (p less than 0.05) increase in clearance from the inner zone as well as from the peripheral zone.

Administration, Oral↗

PubMedDate not supplied

Effect of oral corticosteroids on mucus clearance by cough and mucociliary transport in stable asthma.

Inhaled radioaerosol particles have been used to assess mucus clearance in 12 patients with stable asthma. Patients who coughed frequently showed faster clearance than those who coughed infrequently. Treatment with medium and high dose oral corticosteroids reduced coughing and thereby reliance on mucus transport by cough. Despite this, and despite increased penetration of the particles into the bronchial tree, mean particle clearance was slightly faster after four week treatment (two weeks on 15 mg prednisolone orally each day, plus two weeks on 30 mg). Mean clearance remained, however, markedly slower than in normal subjects. Five patients who were initially sputum producers (mean 1.4 g . h-1) ceased to produce sputum after four week treatment.

Administration, Oral↗

PubMedDate not supplied

Mucus clearance from the airways in chronic bronchitis--Smokers and ex-smokers.

We have assessed lung clearance of inhaled radioactive particles, predominantly deposited in the smaller bronchi, in 60 tests on patients with chronic bronchitis. When tests were matched for sputum production, clearance in ex-smokers was not significantly faster than in patients still currently smoking. Particle clearance also did not depend on FEV1 or--within the range studied--on the depth of particle deposition. Clearance was significantly faster in the patients who coughed frequently and produced high volume of sputum. For some patients with chronic obstructive bronchitis, giving up smoking may lead to poorer mucus clearance because of decreased transport by productive cough.

Aged↗