Archie F. Wilson

Role of Altemaria and Penicillium spores in the pathogenesis of asthma

The ability to harvest spore-rich isolates of molds permitted quantitative studies of their role in the pathogenesis of asthma. Alternaria and Penicillium were selected as examples of ubiquitous molds that readily induce IgE antibodies and are of contrasting sizes. Extracts from those spores were prepared for skin tests and aerosol bronchial challenges. Intact spores were used in the same subjects in bronchial challenges delivered by a Spinhaler. Seven patients with a history of mild asthma received a total of 16 bronchial challenges with the mold to which they had been sensitized. Provocative doses in spore equivalents for a 35% drop in SGaw, 20% drop in FEV1, or 25% drop in PEFR were sought for each challenge. Density dependence-flow rates were also determined. Environmental spore survey data were obtained and compared with the challenge doses for these spores. It was found that immediate-type asthma was readily provoked by both whole spores and by their extracts, in some subjects fewer intact than extracted spores were required, delayed-type asthma occurred only after whole spore challenges, SGaw was the most sensitive and equally specific of the pulmonary function tests, and provocative doses of spore equivalents were within natural exposure ranges. The study confirmed that Alternaria and Penicillium spores in relatively natural states and numbers were potent immunopathogens for asthma.

Thoracoscopic carbon dioxide laser treatment of bullous emphysema

A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation.

Transcendental Meditation and Asthma

A 6-month study with crossover at 3 months was designed to evaluate the possible beneficial effects of transcendental meditation upon bronchial asthma. 21 patients kept daily diaries of symptoms and medications and answered questionnaires at the end of the study and 6 months later. Other measurements included physician evaluation, pulmonary function testing, and galvanic skin resistance. The results indicated that transcendental meditation is a useful adjunct in treating asthma.

Leptin and IGF-I levels in unconditioned male volunteers after short-term exercise.

We have previously shown that serum gonadotropins, particularly LH, decline after acute exercise in male volunteers. The mechanism for this decline is unknown. Plasma leptin and IGF-I concentrations were measured in seven male volunteers after acute exercise to exhaustion using the Bruce protocol. Leptin concentrations declined following exercise reaching nadir values 30-120 min after exercise. As anticipated, plasma IGF-I concentrations showed a transient rise immediately after exercise falling thereafter to nadir levels 60-90 min after exercise before returning towards baseline levels. In view of the previously described decline in gonadotropin release after acute exercise, the decline in plasma leptin levels, perhaps related to the rise in IGF-I, may play a role in exercise-induced inhibition of gonadotropin release presumably by inhibition of GnRH secretion.

Survival after unilateral versus bilateral lung volume reduction surgery for emphysema.

OBJECTIVE Bilateral staple lung volume reduction surgery (LVRS) immediately improves pulmonary function and dyspnea symptoms in patients with advanced heterogeneous emphysema to a greater degree than do unilateral procedures. However, the long-term outcome after these surgical procedures needs to be critically evaluated. We compare 2-year survival of patients who underwent unilateral versus bilateral video-assisted LVRS in a large cohort treated by a single surgical group. METHODS The cases of all 260 patients who underwent video-assisted thoracoscopic stapled LVRS from April 1994 to March 1996 were analyzed to compare results after unilateral versus bilateral procedures. Overall survival was calculated by Kaplan-Meier methods; Cox proportional hazard methods were used to adjust for patient heterogeneity and baseline differences between groups. RESULTS Overall survival at 2 years was 86.4% (95% CI 80. 9%-91.8%) after bilateral LVRS versus 72.6% (95% CI 64.2%-81.2%) after unilateral LVRS (P =.001 for overall survival comparison). Improved survival after bilateral LVRS was seen among high- and low-risk subgroups as well. Average follow-up time was 28.5 months (range, 6 days to 46.6 months) for the bilateral LVRS group and 29.3 months (range, 6 days to 45.0 months) for the unilateral LVRS patients. CONCLUSIONS Comparison of unilateral versus bilateral thoracoscopic LVRS procedures for the treatment of emphysema reveals that bilateral LVRS by video-assisted thoracoscopy resulted in better overall survival at 2-year follow-up than did unilateral LVRS. This survival study, together with other studies demonstrating improved lung function after bilateral LVRS, suggests that bilateral surgery appears to be the procedure of choice for patients undergoing LVRS for most eligible patients with severe heterogeneous emphysema.

A comparison of incremental exercise tests during cycle and treadmill ergometry.

We evaluated a short-duration maximum exercise test by comparing a 15-s incremental exercise protocol with a 1-min incremental method. Twenty normal men and women were studied using cycle and/or treadmill ergometry. In subjects tested on both exercise devices, anaerobic threshold and maximal oxygen uptake (VO2max) were higher for both protocols on the treadmill than on the cycle ergometer (P less than 0.001). However, when the 15-s and 1-min tests were compared using the same device (treadmill or cycle), there were no significant differences between protocols in anaerobic threshold or maximum exercise values of minute ventilation, respiratory rate, tidal volume, VO2max, oxygen pulse, and peak expiratory flow rate. Linear regression analyses indicated differences between the 15-s and 1-min protocols when cardiopulmonary measurements were related to power; however, the two protocols were comparable when cardiopulmonary data were related to oxygen uptake. Comparisons between protocols or between exercise devices were not systematically different in large vs small individuals, or in men vs women. Short-duration incremental exercise tests appear to be reliable, practical methods for assessing exercise performance in normal individuals.

Indirect calorimetry as a guide to caloric replacement during total parenteral nutrition

Fifty patients were studied by indirect calorimetry to assess caloric needs. Seventeen patients received total parenteral nutrition (TPN) in a fixed dose of 45 +/- 3 kcal/kg. Thirty-three patients were studied after acute injury. Indirect calorimetry and the basal energy expenditure equation (BEEE) were compared. In male patients receiving TPN, indirect calorimetry more closely approximated caloric needs than did the BEEE X 1.75. In female patients, the BEEE X 1.75, indirect calorimetry value, and calories infused were more equivalent, and positive nitrogen balance was consistently achieved. In thirty-three trauma patients, indirect calorimetry and the BEEE were compared. Indirect calorimetry consistently predicted higher caloric expenditure than did the BEEE X 1.75. In assessing caloric requirements in acutely catabolic patients, the BEEE X 1.75 appears to be inadequate. The BEEE does not take into account changes in temperature or degree of illness. Indirect calorimetry is easy to perform and gives more pointed information about the patients caloric needs.

Cardiopulmonary effects of long-term bronchodilator administration

Because of reports of drug tolerance occurring with chronic use of adrenergic agents in asthma, we investigated cardiopulmonary responsiveness to ephedrine and to the beta-2 agent, tebutaline, following chronic drug administration for periods up to one year. With chronic drug administration baseline (prior to daily medication) FEV increased 19% in the terbutaline group and 3.5% in the ephedrine group. An additional increase of FEV above baseline of 23% for terbutaline and 12% for ephedrine was noted after daily medication. Terbutaline also had a longer duration of effect; peak response after ephedrine occurred at 2 hr while terbutaline effect was maximal at 3 to 4 hr. There was no evidence for reduced responsiveness to the bronchodilator actions of either drug at any time. Despite prolonged use, both drugs continue to increase heart rate and pulse pressure moderately following ingestion, with a peak effect occurring at 3 hr; however, pulse pressure widened after terbutaline because of a diastolic fall, while the major effect of ephedrine was to increase systolic pressure. Baseline blood pressure, particularly diastolic, declined progressively with continued drug use. No evidence of cardiac, ehpatic, renal, or ophthalmologic toxicity or change in need for other bronchodilator agents was noted during the study with either drug.

Measurement of cardiac output by automated single-breath technique, and comparison with thermodilution and Fick methods in patients with cardiac disease

Accurate noninvasive methods are needed for determination of cardiac output. Current methods are generally complex or may be unreliable. A previously described method, based on absorption of acetylene gas during a constant exhalation that enables calculation of cardiac output by estimating pulmonary capillary circulation, is incorporated in a new, automated commercial product (SensorMedics 2200). In this study, cardiac output by single-breath acetylene blood flow measured with this device was compared with the standard thermodilution and direct Fick methods in 20 patients undergoing cardiac or pulmonary artery catheterization. Patients inhaled test gas mixture to total lung capacity and exhaled at a constant rate through an adjustable resistor. Lung volumes and noninvasive acetylene blood flow value were calculated automatically. Correlation between the automated single-breath technique and both thermodilution and Fick cardiac output determinations was very high (correlation coefficients were 0.90 and 0.92, respectively), regression slopes were close to identity (0.98 and 0.90), and bias (-0.39 and -0.79 liter/min) and precision (0.94 and 1.02) were good; when shunt correction was applied, bias was reduced to 0.06 and 0.35 liter/min, respectively. Rapid, accurate, noninvasive measurement of cardiac output was easily obtained using the automated device. This technique may have a wide applicability for noninvasive evaluation of patients with cardiac disease and for monitoring effects of therapeutic interventions.

The significance of regional pulmonary function changes in bronchial asthma

Abstract Regional ventilation and perfusion relationships were investigated with radioxenon and macroaggregated radioalbumin in thirty-four asthmatic subjects. The results, as well as those of spirometry and blood gas studies, were correlated with the patients symptoms. It was found that all measurements became increasingly abnormal as symptoms increased but were readily reversible with treatment. Areas of hypoventilation generally showed decreased perfusion but perfusion was frequently less affected than ventilation. This ventilation-perfusion imbalance appears to be widespread in asthma and explains the common observation of hypoxemia despite over-all hyperventilation.