Reactance and elastance as measures of small airways response to bronchodilator in asthma.

Bronchodilation alters both respiratory system resistance (Rrs) and reactance (Xrs) in asthma, but how changes in Rrs and Xrs compare, and respond differently in health and asthma, in reflecting the contributions from the large and small airways has not been assessed. We assessed reversibility using spirometry and oscillometry in healthy and asthma subjects. Using a multibranch airway-tree model with the mechanics of upper airway shunt, we compared the effects of airway dilation and small airways recruitment to explain the changes in Rrs and Xrs. Bronchodilator decreased Rrs by 23.0 (19.0)% in 18 asthma subjects and by 13.5 (19.5)% in 18 healthy subjects. Estimated respiratory system elastance (Ers) decreased by 23.2 (21.4)% in asthma, with no significant decrease in healthy subjects. With the use of the model, airway recruitment of 15% across a generation of the small airways could explain the changes in Ers in asthma with no recruitment in healthy subjects. In asthma, recruitment accounted for 40% of the changes in Rrs, with the remaining explained by airway dilation of 6.8% attributable largely to the central airways. Interestingly, the same dilation magnitude explained the changes in Rrs in healthy subjects. Shunt only affected Rrs of the model. Ers was unaltered in health and unaffected by shunt in both groups. In asthma, Ers changed comparably to Rrs and could be attributed to small airways, while the change in Rrs was split between large and small airways. This implies that in asthma Ers sensed through Xrs may be a more effective measure of small airways obstruction and recruitment than Rrs.NEW & NOTEWORTHY This is the first study to quantify to relative contributions of small and large airways to bronchodilator response in healthy subjects and patients with asthma. The response of the central airways to bronchodilator was similar in magnitude in both study groups, whereas the response of the small airways was significant among patients with asthma. These results suggest that low-frequency reactance and derived elastance are both sensitive measures of small airway function in asthma.

A study of artifacts and their removal during forced oscillation of the respiratory system.

Respiratory impedance measured by the forced oscillation technique (FOT) can be contaminated by artifacts such as coughing, vocalization, swallowing or leaks at the mouthpiece. We present a novel technique to detect these artifacts using multilevel discrete wavelet transforms. FOT was performed with artifacts introduced during separate 60 s recordings at known times in 10 healthy subjects. Brief glottal closures were generated phonetically and confirmed by nasopharyngoscopic imaging of the glottis. Artifacts were detected using Daubechies wavelets by applying a threshold to squared detail coefficients from the wavelet transforms of both pressure and flow signals. Sensitivity and specificity were compared over a range of thresholds for different level squared detail coefficients. Coughs could be identified using 1st level detail (cd1) coefficients of pressure achieving 96% sensitivity and 100% specificity while swallowing could be identified using cd2 thresholds of pressure with 95% sensitivity and 97% specificity. Male vocalizations could be identified using cd1 coefficients with 88% sensitivity and 100% specificity. For leaks at the mouthpiece, cd3 thresholds of flow could identify these events with 98% sensitivity and 99% specificity. Thus, this method provided an accurate, easy, and automated technique for detecting and removing artifacts from measurements of respiratory impedance using FOT.

An optical edge detector for the accurate delineation of the light field in radiotherapy machines.

A hand-held detector was developed which allows for the unambiguous and consistent determination of the edge of the light (optical) field on treatment machines conveniently and practically. The design incorporates an electronic circuit using three miniature photodiodes. The complete module is housed conveniently in a hand-held box measuring 6 cm x 10 cm x 1.5 cm. The device eliminates any observer subjectivity on the position of the edge of the light field and hence facilitates greatly any commissioning and quality assurance procedures requiring light-radiation field coincidence. Other applications are possible, including alignment of the light field on patients.

Nuclear multifragmentation, percolation, and the fisher droplet model: common features of reducibility and thermal scaling

It is shown that the Fisher droplet model, percolation, and nuclear multifragmentation share the common features of reducibility (stochasticity in multiplicity distributions) and thermal scaling (one-fragment production probabilities are Boltzmann factors). Barriers obtained, for cluster production on percolation lattices, from the Boltzmann factors show a power-law dependence on cluster size with an exponent of 0.42+/-0.02. The EOS Collaboration Au multifragmentation data yield barriers with a power-law exponent of 0.68+/-0.03. Values of the surface energy coefficient of a low density nuclear system are also extracted.

Evolution of inspiratory and expiratory muscle pressures during endurance exercise.

We investigated the relationship between minute ventilation (VE) and net respiratory muscle pressure (Pmus) throughout the breathing cycle [Total Pmus = mean Pmus, I (inspiratory) + mean Pmus, E (expiratory)] in six normal subjects performing constant-work heavy exercise (CWHE, at approximately 80% maximum) to exhaustion on a cycle ergometer. Pmus was calculated as the sum of chest wall pressure (elastic + resistive) and pleural pressure, and all mean Pmus variables were averaged over the total breath duration. Pmus, I was also expressed as a fraction of volume-matched, flow-corrected dynamic capacity of the inspiratory muscles (P(cap, I)). VE increased significantly from 3 min to the end of CWHE and was the result of a significantly linear increase in Total Pmus (Delta = 43 +/- 9% from 3 min to end exercise, P < 0.005) in all subjects (r = 0. 81-0.99). Although mean Pmus, I during inspiratory flow increased significantly (Delta = 35 +/- 10%), postinspiratory Pmus, I fell (Delta = -54 +/- 10%) and postexpiratory expiratory activity was negligible or absent throughout CWHE. There was a greater increase in mean Pmus, E (Delta = 168 +/- 48%), which served to increase VE throughout CWHE. In five of six subjects, there were significant linear relationships between VE and mean Pmus, I (r = 0.50-0.97) and mean Pmus, E (r = 0.82-0.93) during CWHE. The subjects generated a wide range of Pmus, I/P(cap, I) values (25-80%), and mean Pmus, I/P(cap, I) increased significantly (Delta = 42 +/- 16%) and in a linear fashion (r = 0.69-0.99) with VE throughout CWHE. The progressive increase in VE during CWHE is due to 1) a linear increase in Total Pmus, 2) a linear increase in inspiratory muscle load, and 3) a progressive fall in postinspiratory inspiratory activity. We conclude that the relationship between respiratory muscle pressure and VE during exercise is linear and not curvilinear.

Lack of importance of respiratory muscle load in ventilatory regulation during heavy exercise in humans.

1. Seven active subjects (24 +/- 1 years; maximal oxygen uptake (VO2,max), 3.77 +/- 0.2 l min-1; mean +/- S.E.M.) performed constant work rate heavy exercise (CWHE, approximately 80% of maximal incremental work rate) to exhaustion on 2 days, one with (unload) and one without (control) respiratory muscle unloading. 2. With unloading, a special device applied flow-proportional mouth pressure assist (positive with inspiratory (I), negative with expiratory (E) flows) throughout each breath. No pressure assist occurred during control CWHE. To confirm unloading, respiratory muscle pressures (Pmus) were derived (n = 5) from measured pleural pressure and chest wall elastic and resistive pressures. 3. Other than minor differences in early exercise, the temporal course of minute ventilation (VE) was similar in both tests as exercise progressed. The fall in estimated mean alveolar CO2 (PA,CO2) throughout CWHE was identical in both tests. There were no significant differences (ANOVA) in VE, tidal volume, frequency, oxygen consumption rate (VO2), heart rate or PA,CO2, between unload and control CWHE, at matched times (at 50% of control duration and at the end of exercise). Unloading reduced Pmus significantly throughout CWHE; at 50% control duration, peak Pmus,I and Pmus,E fell by 24 and 41%, respectively, with unloading, as did mean Pmus,I and Pmus,E (21 and 44%). 4. The lack of any significant changes in VE, PA,CO2 or breathing pattern, despite a marked reduction in respiratory muscle load throughout CWHE, indicates that the load on the respiratory muscles has only a minor role in the regulation of ventilation during heavy exercise. 5. The absence of improvement in CWHE duration (control, 11.4 +/- 1.2 min; unload, 12.6 +/- 2.1 min, n.s.) with unloading implies that respiratory muscle function does not limit endurance exercise performance during cycling in healthy humans.

Radiation protection design philosophy for a door interlock system for shared room remote afterloading brachytherapy.

A single remote afterloading system can sometimes be used for the radiation treatment of two or more patients in separate rooms simultaneously. This configuration poses certain radiation protection problems, especially in a busy clinic where some of the treatment rooms have to be used for other non-radiation related patients even though not all radiation treatments have been completed. In this report we describe a door interlock system that has been designed to allow for radiation protection purposes during radiation treatment but is disabled when the radiation treatment is completed--with enough safeguard built in to prevent accidental bypass of the interlock. In addition, the quality control procedures of the radiation monitor devices for these treatment rooms are described. These radiation protection procedures could be generalized to other remote afterloading systems.

Inspiratory muscle weakness in chronic heart failure: role of nutrition and electrolyte status and systemic myopathy.

Inspiratory muscle weakness has been demonstrated in ambulatory, stable chronic heart failure (CHF) and may contribute to dyspnea during daily living. However, the mechanisms underlying this weakness are unknown. Malnutrition and electrolyte depletion are recognized complications of CHF that may impair skeletal muscle function, and limb muscle weakness and myopathic changes have also been demonstrated in CHF. We examined whether nutrition and electrolyte status contribute to the reduced skeletal muscle strength and whether inspiratory muscle weakness in CHF is part of general skeletal muscle weakness. We measured maximum inspiratory and expiratory mouth pressures as indices of respiratory muscle strength, maximum hand-grip strength as an index of limb muscle strength, anthropometric indices, serum albumin, and total lymphocyte count as indices of nutritional status, and serum electrolytes in 15 stable patients with chronic cardiac pump failure who had no evidence of primary lung disease, and in 15 age-and-sex-matched healthy controls. As compared with the matched controls, the CHF patients had reduced inspiratory muscle strength (p < 0.0025), but their expiratory and limb muscle strength were not significantly reduced. CHF patients were not malnourished; they were heavier than matched controls because of increased body fat (p < 0.05). Serum sodium was significantly lower in the CHF patients than in the controls (p < 0.01), but was within the normal range in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Regular inhaled salbutamol and airway responsiveness to allergen.

Regular inhaled beta 2 agonist causes tolerance to the acute protective effect of beta 2 agonist against bronchoconstriction induced by chemical stimuli such as AMP, histamine, and methacholine. We examined a more clinically relevant stimulus, inhaled allergen, in a double-blind, cross-over, random-order trial in 13 mild atopic asthmatics, who had not used beta 2 agonist for at least 4 weeks. We compared regular inhaled salbutamol (200 micrograms four times daily for 2 weeks) with placebo (2 weeks) for effects on bronchodilator response, baseline methacholine, and allergen airway responsiveness, and on the acute protective effect of salbutamol against both stimuli. Baseline forced expiratory volume in 1 s (FEV1), bronchodilator response, and methacholine responsiveness were the same during both treatment periods. After regular salbutamol, the allergen PC20 (provocation concentration producing a 20% FEV1 decrease) fell by 0.91 (SD 0.66) (p = 0.0009) doubling doses, and the protective effects of salbutamol on methacholine and allergen were both significantly reduced (p = 0.026 and 0.025, respectively). Taking into account the reduced baseline allergen PC20, the post-salbutamol allergen PC20 was almost 2 doubling doses (1.94 [1.43], p < 0.01) lower during salbutamol treatment. Thus, 2 weeks of regular inhaled salbutamol increased airway responsiveness to allergen but not to methacholine, and caused tolerance to the protective effect of salbutamol on bronchoconstriction induced by both stimuli. These effects of inhaled beta 2 agonist provide further evidence to support detrimental effects of their regular use.

Engineering modifications for dynamic stereotactically assisted radiotherapy.

To perform dynamic stereotactic radiotherapy, a number of modifications to the commercial linear accelerator were required and these are described in this report. A couch drive system was added to rotate the couch in synchrony with the gantry. A high dose rate beam for this technique is acquired through a head modification, which allows easy removal of the radiation field flattener. Because of these modifications, a number of changes and additions were required to the linac interlock system, including a complete new chain of interlocks for use with the stereotactic technique.

Beclomethasone given after the early asthmatic response inhibits the late response and the increased methacholine responsiveness and cromolyn does not.

BACKGROUND: Single doses of inhaled beclomethasone or inhaled cromolyn, given before allergen inhalation, inhibit allergen-induced late asthmatic responses (LARs) and increased airway responsiveness (delta log methacholine PC20). We hypothesized that when given 2 hours after allergen, beclomethasone might work better than cromolyn. METHODS: In 10 patients with mild, stable, atopic asthma with LARs or delta log PC20 or both, we performed a double-blind, double-dummy, random-order trial comparing a single dose of inhaled beclomethasone (500 micrograms), cromolyn (20 mg), and placebo, administered 2 hours after allergen challenge on LAR and delta log PC20. RESULTS: The treatment effect on LAR was significant (p < 0.001). The LAR after beclomethasone (7.3% +/- 6.1%) was significantly less than after cromolyn (20.4% +/- 15.2%) or placebo (26.4% +/- 8.2%); cromolyn was not different from placebo. There was a borderline treatment effect on delta log PC20 (p = 0.056) with beclomethasone (0.12 +/- 0.31) less than placebo (0.37 +/- 0.39) but not less than cromolyn (0.34 +/- 0.18). CONCLUSION: Beclomethasone (500 micrograms) administered 2 hours after allergen challenge markedly inhibited the LAR and had a small effect on allergen-induced airway responsiveness. Cromolyn (20 mg) was not effective on maximal LAR; a small effect on the early part of the LAR was suggested.

Effect of physical training on breathing pattern during progressive exercise.

It has been suggested that physical training causes a slower, deeper breathing pattern at a given level of ventilation, but there is no convincing evidence to support this. We examined breathing pattern during maximal incremental exercise on a cycle ergometer in 7 males before and after 3-4 weeks of cycle endurance training (TRAINING), and in 6 males before and after a similar period of unaltered physical activity (CONTROL); all subjects were healthy and previously sedentary. After physical training there was a significant increase in peak oxygen uptake, and significant reductions in carbon dioxide output, heart rate (fHR) and minute ventilation (VI) at submaximal workloads; peak VI was significantly increased whereas peak fHR was unchanged. At matched VI levels (moderate, moderately-high, high) the TRAINING subjects' breathing pattern was not significantly altered; there was a power of at least 80% to detect a significant (> 0.30 L) increase in tidal volume (P < 0.05) at moderately high and high ventilation levels. There was no change in the CONTROL subjects' maximal exercise performance, or breathing pattern at matched VI levels, over the same period. Short-term, activity-specific physical training does not significantly affect the breathing pattern adopted by normal humans during progressive exercise.

Miliary Mycobacterium bovis induced by intravesical bacille Calmette-Guérin immunotherapy.

Intravesical instillation of bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the treatment of choice for many patients with bladder cancer. In a small percentage, this therapy is associated with systemic side effects including pneumonitis. It is uncertain whether these systemic manifestations are due to dissemination of infection or due to hypersensitivity, an etiologic distinction that has important therapeutic implications. We report the first case in which miliary M. bovis was proven to be the responsible mechanism, by culture of M. bovis biovar BCG from a transbronchial lung biopsy and complete resolution on anti-tuberculous chemotherapy.

Inspiratory muscle weakness and dyspnea in chronic heart failure.

Dyspnea is a common, disabling symptom in chronic heart failure, yet the underlying mechanisms remain unknown. The respiratory muscle pump is composed of skeletal muscles whose strength directly influences the pump's performance. Respiratory muscle weakness is important in the dyspnea experienced by some patients with pulmonary disease; however, the role of the respiratory muscle pump in the dyspnea of chronic heart failure has not previously been examined. To assess respiratory muscle strength and its relation to dyspnea during daily activity, we measured maximum inspiratory and expiratory mouth pressures as indices of respiratory muscle strength and the baseline dyspnea index in nine stable, chronic cardiac pump failure patients who had no evidence of primary lung disease, and in nine age- and sex-matched healthy control subjects. The chronic heart failure patients, when compared with their matched control subjects, had reduced inspiratory and expiratory muscle strength, and both inspiratory and expiratory muscle strength were significantly correlated with dyspnea during daily activity (r2 = 0.80, p = 0.001 and r2 = 0.45, p = 0.05, respectively). Inspiratory muscle strength accounted for all of the variance in dyspnea that was correlated with respiratory muscle strength when the relative contributions of inspiratory and expiratory muscle strength were examined. There was no correlation between lung volumes or spirometry and dyspnea in the heart failure patients. These findings indicate that patients with stable chronic heart failure have inspiratory and expiratory muscle weakness and further suggest that the respiratory muscle pump significantly contributes to the dyspnea during the activities of daily living.