To determine whether bolus instillation of a mucolytic agent (mesna) could diminish airway resistance, endotracheal tube resistance, or both in patients mechanically ventilated for acute respiratory failure.

A disposable barrier filter (Pall Biomedical, United Kingdom) was developed to prevent the contamination of lung function equipment in clinical use. The aims of this study were to examine its resistance characteristics and to determine the effect of the filter on clinical measurements of lung function.

Although heparin is used as an anticoagulant, its biologic function has remained unclear since the 1920s. Glycosaminoglycan heparin possesses multiple noncoagulant properties, including anti-inflammatory actions, and it is possible that heparin may inhibit airway hyperreactivity. Thus, the purpose of the present investigation was to study the effect of inhaled heparin on methacholine-induced bronchoconstriction. Thirteen subjects (7 women, 6 men) with mild asthma were included in the study. Bronchial provocation tests were performed in a single-blind, crossover, randomized order and repeated 45 min after placebo or aerosolized heparin inhalation (1,000 U/kg). The heparin inhibited bronchoconstriction induced by methacholine. In the methacholine challenge test, heparin treatment resulted in an increase in the mean PD20 over placebo: 5.26 +/- 4.80 mg/mL vs 10.57 +/- 5.72 mg/mL (p < 0.0002). These data suggest that inhaled heparin may have an inhibitory role on methacholine bronchial challenge, possibly via a direct effect on smooth muscle.

The benefit of noninvasive pressure support ventilation (NIPSV) in avoiding the need for endotracheal intubation and reducing morbidity and mortality associated with endotracheal intubation was evaluated in 41 patients who presented with acute respiratory failure not related to chronic obstructive pulmonary disease (COPD). Patients were randomly assigned to receive conventional therapy (n = 20) or conventional therapy plus NIPSV (n = 21). NIPSV was delivered to the patient by a face mask connected to a ventilator (Puritan-Bennett 7200a) set in inspiratory pressure support (IPS) mode. The mean levels of IPS, positive end-expiratory pressure (PEEP), and fraction of inspired oxygen (FIO2) were respectively 15 +/- 3 cm H2O, 4 +/- 2 cm H2O, and 57 +/- 22%. The rate of endotracheal intubation (62 vs 70%, p = 0.88), the length of ICU stay (17 +/- 19 days vs 25 +/- 23 days, p = 0.16), and the mortality rate (33 vs 50%, p = 0.46) were not different between patients treated with NIPSV and those treated conventionally. Post hoc analysis suggested that in patients with PaCO2 > 45 mm Hg (n = 17), NIPSV was associated with a reduction in the rate of endotracheal intubation (36 vs 100%, p = 0.02), in the length of ICU stay (13 +/- 15 days vs 32 +/- 30 days, p = 0.04), and in the mortality rate (9 vs 66%, p = 0.06). We conclude that NIPSV is of no benefit when used systematically in all forms of acute respiratory failure not related to COPD. A subgroup of patients, characterized by acute ventilatory failure and hypercapnia, may potentially benefit from this therapy and further studies are needed to focus on this aspect.

We conducted a randomized clinical trial to evaluate a limited pulmonary rehabilitation program focused on coping strategies for shortness of breath but without exercise training. Eighty-nine patients with COPD were randomly assigned to either 6-week treatment or general health education control groups. Treatment consisted of instruction and practice in techniques of progressive muscle relaxation, breathing retraining, pacing, self-talk, and panic control. Tests of 6-min walk distance, quality of well-being, and psychological function as well as six dyspnea measures were administered at baseline, posttreatment, and 6 months after the intervention. Baseline pulmonary function tests also were obtained. At the end of the 6-week treatment, there were no significant differences between the treatment and control groups on any outcome measure. At the 6-month follow-up, a significant group difference was seen on only one variable, Mahler's transition dyspnea index. The results of this evaluation suggest that a treatment program of dyspnea management strategies, without structured exercise training or other components of a comprehensive pulmonary rehabilitation program, is not sufficient to produce significant improvement in dyspnea, exercise tolerance, health-related quality of well-being, anxiety, or depression.

To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol, 400 micrograms, and ipratropium bromide, 80 micrograms, four times daily administered with a metered-dose inhaler.

Metered-dose inhalers (MDIs) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon (CFC) propellants. The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry. The mean +/- SD relative lung bioavailability of albuterol to the lung following inhalation of 400 micrograms of albuterol from an MDI, the Rotahaler and Diskhaler in 10 well-trained volunteers, was 2.83 (0.78), 1.72 (0.99), and 2.64 (1.23)%, respectively, expressed as a percentage of the nominal dose. The delivery of albuterol to the lungs from the MDI and Diskhaler was similar. In nine asthmatic subjects, the relative lung bioavailability of albuterol following inhalation with the MDI and Diskhaler was 1.19 (0.79) and 2.38 (1.46)%, respectively, expressed as a percentage of the nominal dose. There was no difference in reversibility 30 min after administration of the dose by the two methods. Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique, which was absent in the asthmatic subjects. The Diskhaler does not rely on coordination during inhalation and therefore is easier to use.

To evaluate the effect of inhaled diuretics, furosemide and amiloride, on cough induced by acid inhalation challenge in asthmatic children, a double-blind, randomized, placebo-controlled study was conducted. On separate days, 12 asthmatic children (10.3 +/- 0.7 [SEM] years) underwent acetic acid (AD) inhalation challenge after inhalation of furosemide (10 mg/m2 of body) amiloride (0.3 mg/m2 of body), or placebo (0.9% saline solution). Bronchoconstriction was not observed after administration of furosemide and amiloride. Both inhaled furosemide and amiloride exerted a protective effect against AA-induced cough in asthmatic children (p < 0.01 and p < 0.05, respectively), while there was little correlation between the individual protective potency of furosemide and amiloride against AA-induced cough (rs = 0.344, p = 0.255). These results demonstrate that both furosemide and amiloride can attenuate AA-induced cough, although, this protective effect of inhaled diuretics may not necessarily be dependent on Na(+)-K(+)-Cl- cotransporter or Na+ channel in airway epithelial cells.

Once-daily morning (7 AM) vs evening (10 PM) administration of the terbutaline prodrug bambuterol (20-mg tablet dose) was investigated in a double-blind, cross-over, randomized, and placebo-controlled study involving 29 diurnally active patients with asthma. Terbutaline plasma concentration, spirometry, and drug tolerance were assessed during 39-h inpatient studies. A 7-day washout period separated each treatment. Mean 24-h plasma concentration was comparable for morning and evening bambuterol (13.2 vs 14.0 nmol/L). The Cmax for evening vs morning dosing was 17.2 vs 15.5 nmol/L (p < 0.02). The 24-h mean FEV1 was greater (p < 0.001) for bambuterol (morning: 3.2 L; evening: 3.4 L) vs placebo (2.9 L) as it was for FVC, FEF25-75%, and peak expiratory flow rate (PEFR), with the maximum effect at 4 AM independent of medication time. Evening dosing, however, resulted in greatest 7 AM (awakening) FEV1, FEV25-75, and PEFR (p < 0.03). With reference to corresponding-in-time placebo values, improvement in FEV1 at the end of the 24-h dosing intervals amounted to 0.34 L (13.5%) (p < 0.0004) and 0.35 L (15.9%) (p < 0.0012) with evening and morning bambuterol dosing, respectively. Side effects were greater for bambuterol than placebo, but not significantly so. Once-daily bambuterol therapy proved to be an effective treatment for asthma, whether administered in the evening or morning. Evening dosing seems best for nocturnal asthma since airway patency overnight and on awakening at 7 AM is most improved.

Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5 +/- 5.9 years; FEV1, 0.87 +/- 0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 micrograms ipratropium bromide, (2) 80 micrograms ipratropium bromide, (3) 40 micrograms ipratropium bromide plus 200 micrograms salbutamol, (4) 80 micrograms ipratropium bromide plus 400 micrograms salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV1 responses to combined dosages of 80 micrograms ipratropium bromide and 400 micrograms salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 micrograms salbutamol with 40 micrograms ipratropium bromide compared with 40 micrograms ipratropium bromide alone. Combination therapy with 200 micrograms salbutamol and 40 micrograms ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 micrograms ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 micrograms ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.

To contrast the effectiveness of 2- vs 6-month reevaluation intervals on both clinical outcome and cost in patients requiring continuous home oxygen therapy (HOT).

Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time. Optimal dose and fractionation schemes have not been identified yet. We conducted a prospective randomized study to compare two treatment schedules in terms of survival time, local tumor control, and possible complications.

Although both beta-adrenergic agonists and anticholinergic agents are widely used in the treatment of patients with COPD, they influence the pulmonary circulation and ventilation differently. We compared the effects of these two agents on gas exchange and distribution of ventilation in COPD.

Previous studies on the bronchodilating effect of nitrates yielded conflicting results. We hypothesized that the concomitant bronchial vasodilatation induced by nitrates may limit the increase of airway patency due to bronchial smooth muscle relaxation. To test this hypothesis, we evaluated the bronchodilating effect of nebulized nitroglycerine (NTG), 0.2 mg, in 12 patients with reversible airway obstruction (FEV1 64.3 +/- 8.2% predicted, > 15% increase after salbutamol 200 micrograms by metered-dose inhaler), pretreated with aerosolized norepinephrine (NE) (0.04 mg) or placebo (PL), in a randomized double-blind crossover design, in two separate days. Baseline FEV1 values of the two test days and FEV1 after NE or PL inhalations were not significantly different. After NTG inhalation, FEV1 was 73.8 +/- 7.9% predicted, with NE pretreatment, and 70 +/- 8.2% predicted with PL pretreatment (p < 0.01). The maximal percent increases of FEV1 above baseline were 14.9 +/- 4.8% and 9.2 +/- 2.4%, respectively, after NE and PL pretreatment (p < 0.01). In conclusion, NTG produces a better bronchodilatation when the concomitant vasodilatation is attenuated by a vasocostrictive agent.

In normal conscious humans, when a brief hypoxic ventilatory stimulus is followed immediately by breathing 100% O2, ventilation during hyperoxia gradually declines to baseline prehypoxic levels without an undershoot. During the decline, ventilation is greater than baseline in the absence of hypoxia and hypercapnia. This has been interpreted as evidence of decay of short-term potentiation (STP) or afterdischarge. It is not known whether the intensity of the stimulus that activates STP influences the time course of its decay. Therefore we studied STP decay in nine normal adults after administration of placebo (P) and almitrine (A) in a single-blind manner on 2 separate days. On each day, three runs consisting of 45 s of isocapnic hypoxia (end-tidal PO2 = 55 mm Hg) followed by 2 min of hyperoxia were conducted while ventilation (VI) was measured breath by breath. Baseline VT did not differ between A and P, but at the end of hypoxia, VI with A was 169 +/- 14% (SE) of baseline while VI with P was 132 +/- 7% of baseline (p < 0.05). Immediately after hyperoxia was instituted, VI fell abruptly, the fall being 36% of baseline for A and 15% for P. This probably represented the withdrawal of peripheral chemoreceptor input. Thereafter, VI declined slowly toward baseline, and the time course of this decline did not differ between P and A. Our results indicate that within the limits we studied, the increase of the intensity of the discharge of the peripheral chemoreceptors during hypoxia does not influence STP decay.

To measure the reliability of the assessment of mediastinal lymph node size in computed tomographic (CT) scans of the thorax.

(1) To evaluate a clinical score predicting the early death from Pneumocystis carinii pneumonia (PCP) in HIV-infected patients and to compare it with lactate dehydrogenase (LDH) levels and Karnofsky's performance score. (2) To compare the association of this score and partial oxygen pressure (PaO2) at baseline (at ambiant air) with change in therapy.

Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. In contrast to traditional sclerosing agents, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy, in addition to treating the effusion. The Lung Cancer Study Group evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. Forty-six patients with cytologically proven symptomatic and previously untreated malignant pleural effusions were entered. Cisplatin, as a single dose of 100 mg/m2, plus cytarabine 1,200 mg, were instilled into the pleural space via a chest tube that was then immediately removed. The overall response rate, complete plus partial at 3 weeks, was 49% (18/37 patients). One patient experienced reversible grade 3 renal toxic reactions, four patients had grade 3 hematologic toxic reactions, and five patients had grade 3 cardiopulmonary toxic reactions. Median length of response was 9 months for a complete remission and 5.1 months for a partial remission. Although chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the malignant effusion, intracavitary cisplatin and cytarabine therapy as administered in this trial appears inferior to existing sclerosing agents for the control of malignant pleural effusions. Although administration is safe, it cannot be recommended for the standard control of malignant pleural effusions, but it may have a role incorporated into combination modality therapies for diseases such as malignant pleural mesothelioma.

Between June 1988 and January 1980, 67 patients with pathologic stage III non-small cell lung cancer were randomized to receive either preoperative mitomycin, vinblastine, and cisplatin (MVP) chemotherapy (cisplatin 120 mg/m2, and mitomycin, 8 mg/m2 day 1 + 29, and vinblastine, 4.5 mg/m2 on day 1, 15, 22, and 29 and 2.0 mg/m2 day 8), or preoperative radiotherapy (44 Gy in 22 fractions to the primary tumor and mediastinum). The purpose of this study was to identify a treatment approach that showed sufficient effectiveness and acceptable toxicity to warrant testing by prospective randomized trial against "standard" nonsurgical treatment. All patients had surgical staging of the mediastinum and had either unresectable N2 disease or T4 disease with proximal extension of disease along the pulmonary artery. Response to preoperative therapy was evaluated 8 weeks after beginning treatment and patients with complete or partial radiographic response were to undergo surgical exploration and resection if possible. Fifty-seven patients were eligible and evaluable for response. Of the 67 total patients, 3 were unavailable for follow-up, 4 were ineligible, 1 was canceled, and 2 refused all treatment after having been randomized. Of the eligible and evaluable patients, 49 had stage IIIA and 8 had stage IIIB disease. Randomization was to MVP in 26 cases and to radiotherapy (XRT) in 31. Radiographic response to treatment was virtually identical for the two approaches, with 29 of the 57 evaluable patients achieving objective responses. In patients achieving radiographic response, 24 underwent surgical exploration and 20 underwent resection, of which 18 were complete. The mediastinum was free of tumor in seven patients but only two pathologic complete responses were seen (one each to XRT and MVP). In addition, ten nonresponders underwent surgery; seven underwent resection. Median survival for the entire group is 12 months, with a 27% actuarial survival at 4 years. Two patients died of treatment toxicity during preoperative therapy. Overall toxicity included 2 preoperative toxic deaths and 6 postoperative deaths in 34 patients who underwent surgical exploration (3 each with XRT and MVP) due to adult respiratory distress syndrome (3), myocardial infarction (1), pulmonary edema (1), and esophageal fistula (1), for an overall death rate 8 of 57 (14%) and a perioperative death rate in surgically explored patients of 6/34 (18%). These preoperative regimens, in the population studied herein, were of modest efficacy and substantial toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

To determine the feasibility, toxicity, and potential efficacy of neoadjuvant chemoradiotherapy before surgery in patients with non-small cell lung cancer limited to the chest.