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STUDY OBJECTIVE: Using the negative expiratory pressure (NEP) method, we have previously shown that patients receiving single lung transplantation (SLT) for COPD do not exhibit expiratory flow limitation and have little dyspnea at rest. In the present study, we assessed whether SLT patients exhibit flow limitation, overall hyperinflation, and dyspnea during exercise. METHODS: Expiratory flow limitation assessed by the NEP method and inspiratory capacity maneuvers used to determine end-expiratory lung volume (EELV) and end-inspiratory lung volume (EILV) were performed at rest and during symptom-limited incremental cycle exercise in eight SLT patients. RESULTS: At the time of the study, the mean (+/- SD) FEV(1), FVC, functional residual capacity, and total lung capacity (TLC) amounted to 55 +/- 14%, 67 +/- 12%, 137 +/- 16%, and 110 +/- 11% of predicted, respectively. At rest, all patients did not experience expiratory flow limitation and were without dyspnea. At peak exercise, the maximal mechanical power output and maximal oxygen consumption amounted to 72 +/- 20% and 65 +/- 8% of predicted, respectively, with a maximal dyspnea Borg score of 6 +/- 3. All but one patient exhibited flow limitation and dynamic hyperinflation; the EELV and EILV amounted to 74 +/- 5% and 95 +/- 9% TLC, respectively. The patient who did not exhibit flow limitation during exercise had the lowest dyspnea score. CONCLUSION: Most SLT patients for COPD exhibit expiratory flow limitation and dynamic hyperinflation during exercise, whereas maximal dyspnea is variable.

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This multicentre study was set up to compare the efficacies of two long-acting beta 2-agonists, oral bambuterol (20 mg nocte) and inhaled salmeterol (50 micrograms b.i.d.), for the treatment of moderate to severe asthmatics who were considered to be on optimal steroid/bronchodilator therapy, but continued to have troublesome nocturnal symptoms. The study was of double-blind, parallel-group design and comprised a 2-week run-in on previous maintenance therapy followed by a 6-week study treatment period. There were 117 randomized asthmatic patients aged 20-70 years (65 women and 52 men with a mean age of 45 and predicted FEV1 of 64%), who had been taking 800-2000 micrograms inhaled steroid and/or up to 20 mg oral steroid per day for at least 4 weeks. They were asked to complete daily diary cards, recording morning and evening PEF, daily symptoms, nocturnal awakenings, rescue medication and subjective tremor. There was a significant increase in both morning and evening PEF respectively, on bambuterol (28 l min-1, 20 l min-1, P < 0.05) and salmeterol (29 l min-1, P < 0.001; 23 l min-1, P < 0.01) when compared with run-in. The mean percentage fall in overnight PEF was reduced by 8.3% (P < 0.001) on bambuterol and by 6.8% (P < 0.001) on salmeterol. Nocturnal awakenings and daytime symptoms due to asthma were significantly lowered by both treatments, as was the consumption of rescue bronchodilator. Tremor scores were very low during both run-in and study treatments. No significant treatment difference between bambuterol and salmeterol was detected for any of the above variables. Once-daily oral bambuterol provides a highly effective alternative to twice-daily inhaled salmeterol for relief of nocturnal symptoms in patients with moderate to severe asthma.

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Lung volume reduction surgery in emphysema has, as an objective, the reduction of dyspnoea and an increase in the exercise tolerance in patients with respiratory insufficiency suffering from diffuse emphysema. In principle the resection of the most diseased areas of emphysema leads to improvement in the mechanical properties of the emphysematous lung and correct pulmonary hyperinflation. The respiratory function benefits both objective and subjective, produced by surgery are real but transitory and inconstant depending in particular on the evolutionary profile of the emphysematous disease. The indications should be further refined and an objective comparison of different surgical techniques has not been achieved. The impact on the quality of life for these patients is unknown.

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Application of negative pressure at the mouth during tidal expiration (NEP) provides a simple, rapid, noninvasive method for detecting expiratory flow limitation during spontaneous breathing. Patients in whom NEP elicits an increase in flow throughout expiration are not flow-limited (FL). In contrast, patients in whom application of NEP does not elicit an increase in flow during most or part of tidal expiration are considered FL. We have used the NEP technique to assess the prevalence of expiratory flow limitation during resting breathing in sable asthmatic patients in both the seated and supine positions. In patients in the sitting position, we have also assessed flow limitation with the conventional method, based on comparison of tidal and maximal expiratory flow-volume (MEFV) curves. We studied 13 patients (FEV1 range: 48 to 94% predicted) with both the NEP and conventional techniques. According to the NEP technique, none of the patients was FL in the seated and only two were FL in the supine position. By contrast, on the basis of the conventional method, six of the patients would have been classified as FL in the sitting position. We conclude that: (1) most stable asthmatic patients do not exhibit tidal expiratory flow limitation during resting breathing; and (2) the conventional method for assessing flow limitation may lead to erroneous conclusions.

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Expiratory flow limitation and dyspnea during resting breathing are common in patients with severe chronic obstructive pulmonary disease (COPD). Although single lung transplantation (SLT) is used to treat end-stage COPD, its effects on flow limitation and dyspnea are not well established. We assessed expiratory flow-limitation and dyspnea in 13 COPD patients after SLT at rest in the sitting and supine positions by applying negative pressure at the mouth during tidal expiration (negative expiratory pressure [NEP] technique). If NEP increases flow throughout the control tidal volume (VT), flow limitation is absent (not flow limited [NEL]). If NEP does not increase flow during part of the control VT, flow limitation is present. After SLT, lung function improved in all but one patient. Twelve patients were NFL during resting breathing in both positions studied. The patient whose lung function did not improve after SLT was flow-limited (FL) both when seated and supine. This patient also exhibited moderately severe chronic dyspnea (Medical Research Council [MRC] score = 3). In the nine other patients in whom dyspnea was assessed, it was slight (MRC score = 1). In conclusion, after SLT for end-stage COPD, expiratory flow limitation at rest is uncommon in both the seated and supine positions. This is consistent with the finding that after SLT the degree of chronic dyspnea is generally slight.

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Recently, latent pulmonary involvement has been described in adult patients with inflammatory bowel disease. It is unknown, however, whether this also occurs in children, and whether the pulmonary abnormalities differ between the acute phase and remission. The incidence of pulmonary abnormalities has been investigated in 26 children with acute or quiescent Crohn's disease in terms of the following parameters: clinical pulmonary symptoms, chest roentgenograms and pulmonary function tests, including lung transfer factor for carbon monoxide (TLCO). One child had a severe digital clubbing. Chest radiographs were normal in all subjects. No significant differences were found between acute and quiescent phase for pulmonary volumes and expiratory flows, but TLCO (% predicted) was significantly decreased during the active phase of the disease as compared to remission (53 +/- 15 vs 81 +/- 19% predicted). These data suggest that latent pulmonary involvement is also present in a paediatric population with active Crohn's disease, despite a short disease history and absence of smoking. Although the nature of this abnormality remains unclear, this extradigestive epiphenomenon should be taken into account with respect to the aetiopathogenesis of Crohn's disease.

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The effects of malnutrition and refeeding on nutritional indices, pulmonary function, and diaphragmatic contractile properties were studied in severely malnourished patients with anorexia nervosa. Fifteen patients were evaluated upon hospital admission (Day 0) and on Days 7, 30, and 45 after starting feeding. Spirometry, lung volumes, and arterial blood gases were measured at each time interval, as were contractile properties of the diaphragm as assessed by transdiaphragmatic pressure generated during electrical phrenic nerve stimulation (Pdistim) and a maximal sniff maneuver (Pdisniff). Anthropomorphic and biochemical measurements were performed at each time interval. Patients were severely malnourished upon admission; mean body weight was 37.1 +/- 4.7 kg (63% ideal body weight). During nutritional support, body weight increased significantly to 42.9 +/- 4.6 kg on Day 45 (p < 0.01), as did muscle mass: 11.2 +/- 4.1 kg on Day 0, to 16.6 +/- 4.9 kg on Day 45 (p < 0.01). Vital capacity and FEV1 increased significantly by Day 30 (p < 0.05). Lung volumes were unchanged. Mean arterial blood gas values were also within the normal range at Day 0; PaO2, 92.6 +/- 2.4 mm Hg and PacO2, 41.0 +/- 1.5 mm Hg. Four patients, however, had an increased PacO2 (> 42 mm Hg) at Day 0, which returned to normal by Day 30. Diaphragmatic contractility was severely depressed initially; Pdistim, 15.9 +/- 1.4 cm H2O; Pdisniff, 65.4 +/- 5 cm H2O; but it significantly increased with nutritional support by Day 30 to 22.5 +/- 1.9 and 84.6 +/- 4.7 cm H2O, respectively. We conclude that diaphragmatic function is severely impaired in malnuorished patients free of other coexisting

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BACKGROUND: The increased use of high dose inhaled steroid in the treatment of asthma has revealed the risk of dose-dependent side effects. Nedocromil sodium is a non steroidal agent with anti-inflammatory properties. OBJECTIVE: To demonstrate whether nedocromil sodium may have some therapeutic benefit in asthmatic patients treated with high dose inhaled steroids and whether it has an inhaled steroid sparing effect. PATIENTS: 134 adults with moderate to severe asthma not adequately controlled with high dose inhaled steroids (750 to 1,500 micrograms/day). METHOD: After a two week baseline period, patients were randomized to receive either nedocromil sodium (4 mg qid) or placebo for 24 weeks in a double blind fashion. During the first 12 weeks of treatment, the dose of inhaled steroid was maintained constant whereas it was altered during the last 12 weeks according to asthma scores. RESULTS: Among 108 patients reaching the reduction phase, a decrease of 250 micrograms of inhaled steroid or more was possible in 79% of patients on nedocromil sodium and in 60% of patients on placebo (p < 0.03). Symptoms scores were improved on both treatments during the 12 first weeks, more on nedocromil sodium than on placebo, treatment difference reaching significance for daytime asthma (p < 0.02). FEV1 improved during the trial for patients on nedocromil (from 69 +/- 18% to 74 +/- 21%; p < 0.005) whereas it did not for those on placebo. CONCLUSION: Nedocromil sodium is effective in improving moderate to severe asthma in addition to inhaled steroid and has some steroid sparing effect in patients treated with high dose inhaled steroid.

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Patients with severe chronic obstructive pulmonary disease (COPD) commonly complain of insomnia, but hypnotic drugs are generally not recommended due to their depressant effect on the respiratory centres. The aim of this study was, therefore, to compare the effects of a single dose of the benzodiazepine hypnotics, triazolam 0.25 mg and flunitrazepam 1 mg, and a new imidazopyridine compound, zolpidem 10 mg, in hypercapnic COPD patients. Twelve stable COPD patients (mean +/- SD arterial oxygen tension (PaO2) 9.3 +/- 0.8 kPa and arterial carbon dioxide tension (PaCO2) 5.9 +/- 1.9 kPa) were included in the study. The following measurements were performed before and 2 h after drug administration: PaO2 and PaCO2, minute ventilation (VE), mouth occlusion pressure (P0.1), rebreathing CO2 tests with ventilatory response to carbon dioxide stimulation (delta VE/delta PACO2) and mouth occlusion pressure response to carbon dioxide stimulation (delta P0.1/delta PACO2). The measurements were performed in a randomized, double-blind fashion, each patient receiving a single dose of each drug on three different days, separated by a one week interval. No difference was noted between control measurements and those taken 2 h after administration of zolpidem in the following parameters: PaCO2, PaCO2, VE, P0.1, delta VE/delta PACO2 and delta P0.1/PACO2. Two hours after administration of triazolam and flunitrazepam, a significant difference was noted in VE for triazolam and for flunitrazepam. After flunitrazepam administration, a significant decrease in PaCO2 (6 +/- 1.8 at baseline versus 7 +/- 0.4 kPa), and delta VE/PACO2 (0.44 +/- 0.20 at baseline versus 0.31 +/- 0.21 l.min-1 x kPa) were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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We have studied the mode of ventilation and chemosentivity in 10 patients suffering from pulmonary fibrosis. The total lung capacity was on average 63.5 +/- 8% of the predicted. Their static compliance was 0.078 +/- 0.05 l.cm of water. The patients were studied in the prone position breathing ambient air then on hyperoxia. The response to CO2 was assessed according to the rebreathing method of Read. The results of these patients were compared with those of 11 normal subjects. The ventilation at rest was normal, with a shortened respiratory time and a Ti/Ttot ratio which was lowered. The occlusion pressure (P0.1) was very much higher than that in normal subjects. This rise was correlated with an increase in pulmonary elastance and a reduction in vital capacity. The correction of hypoxia was without effect on the respiratory parameters. In relation to normal subjects the ventilatory response to carbon dioxide in fibrotics was decreased whilst the response of the P0.1 was increased expressing central hyperactivity. In conclusion, fibrotic patients have normal ventilation in spite of an increase in inspiratory work. This normal ventilation results from hyperactivity of the respiratory centre, as in the hyperventilation induced by carbon dioxide when at rest.

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We have investigated the transition from apnoea to spontaneous breathing in five comatose patients self intoxicated with barbiturates and carbamates. All patients were apnoeic on admission, and were studied throughout the course of recovery. The transition between the first respiratory movements and a stable and nearly normal ventilation (stable respiratory activity) ranged from 15 to 105 min, a very short time compared to the duration of the apnoeic state that lasted 6 to 72 h from admission. Minute ventilation and occlusion pressure during the first respiratory movements were 6.3 +/- 2.7 l.min-1 and 1.35 +/- 0.45 kPa, respectively. These values increased by roughly 50 and 100% by the time stable respiratory activity was achieved. The increase in minute ventilation was entirely due to an increased inspiratory flow, in relation to a proportionate increase in occlusion pressure, and without significant changes in the respiratory times or in the effective elastance. We conclude that the transition between apnoea and stable respiratory activity is characterized by its rapidity, by the fact that respiratory times are fixed throughout the recovery process, and by the fact that effective elastance is high.

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We have investigated the respiratory response to CO2 and to O2 in comatose subjects self intoxicated with barbiturates and carbamates. The chemical drive of 12 such patients with coma was compared with that of comparable normal subjects. The ventilatory response to CO2 was depressed but the P0.1 response was of the same order of magnitude as in normals. O2 had little effect on the ventilatory parameters and occlusion pressure. There was no difference between the two groups of patients, indicating that the respiratory changes observed were more dependent on the intensity of the intoxication than on the nature of the drugs. In addition, mechanical factors seem mainly responsible for the depressed ventilatory response to CO2.

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To assess the effects of theophylline in chronic obstructive pulmonary disease, we conducted a randomized, placebo-controlled, double-blind, crossover trial in 60 patients with severe but stable disease. The patients (mean age, 61 years) were studied before and after two months of placebo and two months of treatment with a sustained-release preparation of theophylline (10 mg per kilogram of body weight per day), administered orally. The two treatments were administered in a random order and separated by an eight-day washout period. After taking theophylline for two months (mean plasma concentration, 14.8 mg per liter), as compared with the two months of placebo, the patients had significant improvements in dyspnea, pulmonary gas exchange (partial pressure of arterial oxygen, 66 vs. 61 mm Hg [P less than 0.0001]; partial pressure of arterial carbon dioxide, 44 vs. 49 mm Hg [P less than 0.0001]), vital capacity (63 percent vs. 58 percent of the predicted value [P less than 0.0001]), and forced expiratory volume in one second (36 percent vs. 32 percent of the predicted value [P less than 0.0001]), with no significant change in airway resistance or functional residual capacity. Minute ventilation increased by a mean of 18 percent (P less than 0.0001) in the patients taking theophylline because of increased tidal volume, with no change in respiratory frequency. The respiratory-muscle performance of the patients taking theophylline improved by approximately 29 percent (P less than 0.0001), as indicated by a decline in the ratio of inspiratory pleural pressure during quiet breathing to maximal pleural pressure. We conclude that theophylline improves respiratory function and dyspnea in patients with severe chronic obstructive pulmonary disease and that these improvements are probably due to better respiratory-muscle performance.

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STUDY OBJECTIVE: To assess the effects of dopamine, which has an inotropic effect on the myocardium and increases renal and splanchnic blood flow, on diaphragmatic contraction. DESIGN AND PATIENTS: We studied the changes in transdiaphragmatic pressure during electrical bilateral supramaximal stimulation of the phrenic nerves in eight patients with chronic obstructive pulmonary disease during acute respiratory failure. In three patients, changes in diaphragmatic blood flow were also evaluated. METHODS: All patients were intubated and artificially ventilated. Stimulated transdiaphragmatic pressure, cardiac output, evaluated with a Swan Ganz catheter, and diaphragmatic blood flow, evaluated by timed volume collections of left phrenic venous effluent (a catheter was introduced into the right femoral vein and advanced into the left inferior phrenic vein) were measured before dopamine infusion, every 10 minutes after the onset of dopamine infusion (10 micrograms/kg body weight.min during 30 minutes) and 15 minutes after the end of dopamine infusion. Arterial blood gases and pH were measured before and at the end of dopamine infusion. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and pH were maintained within normal range by mechanical ventilation throughout the study. With dopamine infusion, heart rate increased by 17% (P less than 0.001) and cardiac output by 40% (P less than 0.001) on the average. The increase in cardiac output was accompanied by a marked increase in diaphragmatic blood flow (30% on the average) in the three patients in whom it was measured (P less than 0.001). Diaphragmatic strength also increased significantly during dopamine administration. Transdiaphragmatic pressure for an identical phrenic stimulation increased by 30% (P less than 0.001) on the average. The changes in cardiac output, diaphragmatic blood flow, and transdiaphragmatic pressure persisted throughout the infusion period; all values returned to control values 15 minutes after the end of dopamine administration. CONCLUSIONS: Dopamine has a potent effect on diaphragmatic strength generation and diaphragmatic blood flow in patients with chronic obstructive pulmonary disease during acute respiratory failure. It is possible to improve diaphragmatic contraction in these patients by administering pharmacologic agents that augment diaphragmatic blood flow.

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The effects of a 3-day pneumococcal infection on diaphragmatic strength and endurance capacity were studied in an in vivo rat model. Thirty-four rats were divided into a control (C) (n = 17) or a septic (S) group (n = 17). Animals were inoculated subcutaneously with 10(11) Streptococcus pneumoniae (S), or sterile culture media (C). All rats were studied 3 days after inoculation. Diaphragmatic strength and endurance capacity were studied in 11 animals of each group. Diaphragmatic strength was assessed by measuring transdiaphragmatic pressure (Pdi) generated during electrical stimulation of the phrenic nerves at different frequencies (0.5, 10, 20, 30, 50, and 100 Hz). Endurance index was calculated as the ratio of Pdi generated after 30 s of phrenic nerve stimulation at 10 Hz divided by the initial force. Measurements of lung weights and lung histologic examinations were performed in the 6 remaining rats from each group. S animals were hyperthermic (39 to 40 degrees C rectal temperature). There was no evidence of pneumonia at histologic examination in Group S. No differences in wet weight of the lung and in the dry-to-wet weight ratio were noted in Group S as compared with Group C. However, S. pneumoniae was isolated from blood and lungs of S animals. Diaphragmatic weight was not different between S and C groups, whereas the weights of the extensor digitorium longus (EDL), tibialis anterior (TA), and soleus muscles were significantly reduced in Group S as compared to Group C.(ABSTRACT TRUNCATED AT 250 WORDS)

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