The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): hypothesis and design. BRONCUS-trial Committee.

Chronic obstructive pulmonary disease (COPD) is an irreversible disorder characterized by airflow obstruction and a progressive decline in forced expiratory volume in one second (FEV1). At present, no treatment except quitting smoking appears to affect the progression of the disease. Oxidative stress has been implicated in its pathogenesis. The Bronchitis Randomized on NAC Cost-Utility Study (BRONCUS) is a phase III, randomized, double-blind, placebo-controlled, parallel group, multicentre study designed to assess the effectiveness of the antioxidant agent N-acetylcysteine (NAC) in altering the decline in FEV1, exacerbation rate, and quality of life in patients with moderate to severe COPD. In addition, cost-utility of the treatment will be estimated. Patients will be followed for 3 yrs and evaluated every 3 months. The necessary sample size to demonstrate an effect on the decline in FEV1 of 20 mL x yr(-1) was estimated to be 478 patients. Five hundred and twenty-three patients with moderate to severe COPD were recruited from 10 European countries from June 1, 1997-December 31, 1999. They were 63+/-8 yrs old and consisted of 243 (46%) current smokers and 280 (54%) exsmokers. Patients had on the average 4.9+/-1.6 exacerbations during the last 2 yrs. Postbronchodilator FEVI averaged 57+/-9% and the reversibility after 400 microg of Salbutamol averaged 4+/-4% predicted. The final results of the trial will be available in about 2 yrs. The study will provide objective data on the effects of N-acetylcysteine on outcome variables in chronic obstructive pulmonary disease.     

Response to oral corticosteroid in patients with chronic obstructive pulmonary disease.

We studied the effect of 30 mg of prednisolone on 29 Japanese patients with chronic obstructive pulmonary disease (COPD). The mean value of the baseline forced expiratory volume in one second (FEV1; mean +/- SEM) was 1.14 +/- 0.12 l (46.9 +/- 3.9% pred) and the FEV1 following the steroid trial was 1.30 +/- 0.12 l (53.7 +/- 4.3% pred). Post-trial FEV1--baseline FEV1/predicted FEV1 was 6.8 +/- 1.9%. Five patients (17%) had more than a 15% increase in FEV1 as a percentage of predicted FEV1. Post-trial FEV1/baseline FEV1 was 117.3 +/- 4.3%, and 12 patients (41%) had more than a 20% increase in FEV1 after the trial. Acute bronchodilator response to beta-agonist correlated positively with the response to corticosteroid. Baseline spirometries, blood eosinophil counts, serum IgE levels, sputum eosinophil counts, family history of asthma, and history of paroxysmal dyspnea did not vary across responders and non-responders. Patients with severe COPD should be treated to achieve the best possible pulmonary functions indicated by a steroid trial within the limit of acceptable levels of adverse effects.     

N-acetylcysteine in cystic fibrosis and Pseudomonas aeruginosa infection: clinical score, spirometry and ciliary motility

The effect of peroral N-acetylcysteine (NAC) in patients with cystic fibrosis (CF) and chronic pulmonary Pseudomonas aeruginosa infection was studied in 52 patients in a double-blind, placebo-controlled, cross-over trial of two, 3 month durations. Active treatment consisted of NAC, 200 mg x 3 daily (patients weighing less than 30 kg) or 400 mg x 2 daily (greater than 30 kg). The effect was evaluated by a subjective clinical score, weight, sputum bacteriology, blood leucocyte count, sedimentation rate, titres of specific antimicrobial antibodies, lung function parameters and measurement of nasal ciliary function in vitro. 31 patients completed the study. No significant differences in lung function or subjective clinical scores were seen between NAC and placebo for the study group as a whole. Patients with peak expiratory flow rate (PEFR) below 70% of predicted normal values showed a satisfactory significant increase in PEFR, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) during NAC treatment. No effect of NAC on ciliary activity was observed.     

Decline in FEV1 related to smoking status in individuals with severe alpha1-antitrypsin deficiency (PiZZ).

Severe alpha1-antitrypsin (AAT) deficiency predisposes to emphysema development. Highly variable rates of decline in lung function are reported in PiZZ individuals. The annual decline in forced expiratory volume in one second (FEV1; delta FEV1) was analysed in relation to smoking status in a cohort of 608 adult PiZZ individuals included in the Swedish national AAT deficiency register. Delta FEV1 was analysed in 211 never-smokers, in 351 exsmokers, and in 46 current smokers after performing at least two spirometries during a follow-up time of 1 yr or longer (median 5.5 yrs, range 1-31). The adjusted mean delta FEV1 in never-smokers was 47 mL x yr(-1) (95% confidence interval (CI) 41-53 mL x yr(-1)), 41 mL x yr(-1) (95% CI 36-48 mL x yr(-1)) in exsmokers, and 70 mL x yr(-1) (95% CI 58-82 mL x yr(-1)) in current smokers. A dose-response relationship was found between cigarette consumption and delta FEV1 in current smokers and exsmokers. In never-smokers, a greater delta FEV1 was found after 50 yrs of age than before. No sex differences were found in delta FEV1. In conclusion, among PiZZ individuals, the change in forced expiratory volume in one second is essentially the same in never-smokers and exsmokers. Smoking is associated with a dose-dependent increase in the change in forced expiratory volume in one second.     

Factor V leiden homozygosity, dyspnea, and reduced pulmonary function

BACKGROUND: Factor V Leiden homozygosity predisposes patients to deep venous thrombosis and major pulmonary thromboembolism. Consequently, factor V Leiden homozygosity could, via unrecognized repeated minor pulmonary thromboemboli, cause chronic pulmonary disease. We tested the hypothesis that factor V Leiden homozygosity is associated with pulmonary symptoms and signs. METHODS: We studied a general population sample of 9253 individuals from the Copenhagen City Heart Study who were examined in 1991-1994. Of these, 6475 participants were also examined in 1976-1978 and/or 1981-1983. End points were dyspnea and lung function. RESULTS: Among 20 factor V Leiden homozygotes, a mean +/- SD of 32% +/- 11% had severe dyspnea compared with 6% +/- 0.3% of 8534 noncarriers (chi(2) test; P<.001). The corresponding adjusted odds ratio for severe dyspnea was 5.4 (95% confidence interval, 1.9-15.7). During follow-up, forced expiratory volume in 1 second and forced vital capacity were 5% to 10% lower in homozygotes vs noncarriers (analysis of variance; P = .003 and P = .03). The annual mean +/- SD loss of forced expiratory volume in 1 second and forced vital capacity was 39 +/- 8 mL/y and 35 +/- 8 mL/y in homozygotes vs 21 +/- 10 mL/y and 15 +/- 10 mL/y in noncarriers (t test; P = .03 and P = .04), respectively. Factor V Leiden heterozygosity (n = 699) did not influence pulmonary symptoms and signs. CONCLUSION: We demonstrate a previously unrecognized clinical presentation of factor V Leiden homozygosity with severe dyspnea and decreased pulmonary function.     

Efficacy of fluticasone propionate compared with beclomethasone dipropionate in bronchial asthma: improvement in compliance and symptoms by fluticasone.

Recent studies have shown that fluticasone propionate (FP) was more effective than beclomethasone dipropionate (BDP) inhalation even at a dose reduced by twofold or more in the treatment of bronchial asthma. Here, we further compared the effectiveness of FP and BDP, including rates of drug compliance. Forty-two symptomatic patients were treated by BDP (1000 +/- 345; mean +/- SD; microgram/day) for 8 weeks, followed by FP at one-half the respective dose, and peak expiratory flow and forced expiratory volume in 1 second were investigated. In addition, the patients were asked about drug compliance and factors related to compliance (expressed using a visual analogue scale). Significant increases of peak expiratory flow (from 316 +/- 96 L/minute to 345 +/- 86 L/minute) and forced expiratory volume in 1 second (from 1.7 +/- 0.5 L to 1.9 +/- 0.4 L) were found. Furthermore, significantly higher scores were obtained for compliance and various factors related to compliance. These data indicate that FP is more effective than a twofold higher dosage of BDP and that better compliance with the use of FP, probably because of improved various factors associated with FP compliance, contributes to FP efficacy.     

N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis.

N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p<0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.     

Improved quality of life after lung volume reduction surgery.

Lung volume reduction surgery (LVRS) improves dyspnoea, pulmonary function, and physical performance in patients with severe pulmonary emphysema. This study investigated the impact of LVRS on health-related quality of life (HRQL) over a 2-yr period following surgery. Thirty-nine consecutive patients were prospectively assessed before LVRS, and followed over 24 months postoperatively. The assessments included pulmonary function, dyspnoea (Medical Research Council (MRC) dyspnoea score), 6-min walking distance (6MWD) and HRQL using the Short Form 36-item questionnaire (SF-36). Several domains of SF-36 improved considerably over 2 yrs after surgery: Physical Functioning: 39 +/- 4 (mean +/- SEM) versus 16 +/- 2 (p<0.01); Vitality: 51 +/- 3 versus 32 +/- 3 (p<0.01); Social Functioning: 72 +/- 4 versus 51 +/- 5 (p<0.01). Also, improvements in pulmonary function (forced expiratory volume in one second (FEV1): 27 +/- 1% predicted, residual volume (RV)/total lung capacity (TLC): 0.65 +/- 0.01), 6 MWD (274 +/- 16 m) and dyspnoea (MRC: 3.9 +/- 01) were sustained for up to 2 yrs after LVRS (FEV1 36 +/- 2% pred, RV/TLC: 0.58 +/- 0.02; 6 MWD: 342 +/- 19 m; MRC: 2.0 +/- 0.2; p<0.05). In patients with severe emphysema, lung volume reduction surgery had positive effects on health-related quality of life and pulmonary function over 2 yrs.     

Air travel in patients with chronic obstructive pulmonary disease

Air travel exposes patients with chronic obstructive pulmonary disease to the risk of severe hypoxemia. We sought to determine the frequency and outcome of airline travel in patients with chronic obstructive pulmonary disease. A cohort of 100 patients (76 men and 24 women; age 67 +/- 7 years [mean +/- SD]) with severe chronic pulmonary obstructive disease examined by means of spirometry (forced expiratory volume in the first second, 0.04 +/- 0.35 L), all military retirees, or their dependents, comprised the study population. Forty-four patients traveled by commercial air carrier over a 28-month interval, giving an annual frequency of 18.9% of these patients per year. The group that did not travel by air (n = 56) had a lower mean value for forced expiratory volume in the first second and greater prevalence of home oxygen use than did the group that did travel by air. Twelve of the travelers (27.3%) consulted a physician beforehand. Flights reached foreign destinations for 22.7% of patients. The median duration of the longest flight segment was 3 hours. A minority of patients (34.3%) occupied seats in the smoking sections of aircraft. A majority (56.8%) ambulated aboard the aircraft during flights. Eight patients (18.2%) reported transient symptoms during air travel. We conclude that patients with chronic obstructive pulmonary disease travel with appreciable frequency, often without medical consultation, and develop symptoms in some cases.     

Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room

The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one-second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy.     

Evaluation of bronchodilator responses in patients with "irreversible" emphysema.

Given the emerging physiological and clinical rationale for pharmacological lung-volume reduction, assessment of volume responses to bronchodilators is likely to be highly relevant in chronic obstructive pulmonary disease (COPD). The authors examined the magnitude of lung-volume reduction after acute bronchodilator treatment in patients with advanced emphysema. Eighty-four stable patients with emphysema (mean+/-SEM forced expiratory volume in one second (FEV1): 32+/-1% predicted) performed spirometry and body plethysmography before and 15-30 min after 200 microg salbutamol. Only irreversible patients with a postbronchodilator change in FEV1 <10% pred were considered in this study. Postsalbutamol, the majority of subjects (83%) had significant improvements in one or more lung volumes: on average, residual volume (RV), functional residual capacity (FRC), inspiratory capacity (IC), forced vital capacity and slow vital capacity changed by -18+/-2, -10+/-1, 8+/-1, 9+/-1 and 7+/-1% pred (p<0.0005 each). Total lung capacity (TLC) decreased 0.12+/-0.04 L (p<0.01). Change in IC reflected change in FRC (r=-0.60, p<0.0005), but more strongly in the 57% of patients with no significant change in TLC (r=-0.93, p<0.0005). The magnitude and frequency of volume responses were greatest in patients with the most severe COPD; for example, RV decreased by 0.51+/-0.09 L (23+/-4% pred) and 0.27+/-0.04 L (14+/-2% pred) in severe and moderate subgroups, respectively. Significant reductions in lung hyperinflation occurred in the absence of a change in forced expiratory volume in one second after low-dose salbutamol in a majority of patients with advanced emphysema; the greatest changes occurred in those with the most severe disease.     

Effects of long intubation period on respiratory functions following open heart surgery

The objective of the present study was to compare pre- and postoperative pulmonary function tests in adult patients who had intubation periods greater and less than 24 hours following elective open heart surgery. Group 1 consisted of 91 patients (18 females and 73 males) gr, whose intubation periods were more than 24 hours (mean: 8.1+/-18.6 hours); and group 2 75 patients (13 females and 62 males) who had intubation periods less than 24 hours (mean: 13.25+/-3.60 hours). The pulmonary function test measurements were obtained from a vitalograph before and after the operation (just before being discharged from the hospital), All patients underwent cardiopulmonary physiotherapy and a rehabilitation programme during their hospital stay. The patients were similar in height and weight. The duration of hospitalization of the patients who had a prolonged intubation period was 17.26+/-9.7 days, while that of the control group was 10.64+/-2.04 days (P<0.0001). When the preoperative pulmonary function test values of each patient were compared with the expected values, the percent values of forced expiratory volume for one second, flow velocity of the mid-forced expiration and forced expiratory flow which were achieved by group 2 were significantly high compared to those of group 1 (P=0.014, P= 0.03 and P<0.0001, respectively). However, the percent values of forced vital capacity were similar. When the percent variations of the differences between the pre- and postoperative pulmonary function test values of the groups were compared, all values except the flow velocity of the mid-forced expiration, and forced vital capacity, were found to be significantly lower statistically in the group having a prolonged intubation period. As a result, it was determined that the patients whose preoperative pulmonary function test values were poor, had longer intubation periods and similarly, they continued to be worse after the operation. We believe that it is advantageous to apply more intensive pulmonary rehabilitation for prolonged periods to these patients in the postoperative period.     

Comparison of N-acetylcysteine and fenoldopam for preventing contrast-induced nephropathy (CAFCIN)

BACKGROUND: N-acetylcysteine and fenoldopam are commonly prescribed for prevention of contrast mediated nephropathy, however, comparative superiority of either agent is unknown. METHODS: In a prospective, randomized, parallel-group trial, adult cardiac catheterization patients at the university and veterans' hospitals with pre-existing stable renal insufficiency were randomized to N-acetylcysteine 600 mg orally twice daily for 4 doses or fenoldopam 0.1 mcg/kg/min intravenously for a minimum of 8 h. All patients received intravenous hydration with normal saline (5% dextrose in normal saline for diabetics on insulin). Randomization was stratified for diabetes. The primary endpoint was mean change in Scr at 72 h. Secondary endpoint was the incidence of contrast-induced nephropathy (25% increase above baseline Scr or absolute increase of 0.5 mg/dL). RESULTS: Study termination occurred after ninety-five patients (mean age 68+/-10 years, female 25%, diabetic 42%, mean baseline Scr 1.5+/-0.4 mg/dL) were randomized, with 84 completing follow-up (44 N-acetylcysteine, 40 fenoldopam). Overall, there were no significant differences in mean change in Scr at 72 h (N-acetylcysteine 0.20+/-0.72 vs. fenoldopam 0.08+/-0.48 mg/dL, p=0.4) or incidence of contrast-induced nephropathy (N-acetylcysteine 5 vs fenoldopam 8, p=0.4). No differences were detected in subgroup analyses for diabetes, baseline Scr >1.7 or 2.0 mg/dL, gender, age >70 years, or contrast volume >150 mL. Results were similar after multivariate adjustment for diabetes, contrast volume, heart failure and gender. CONCLUSIONS: Our randomized comparison failed to demonstrate a significant difference in the abilities of N-acetylcysteine and fenoldopam to prevent the decline in renal function or the incidence of contrast-induced nephropathy during cardiac catheterization.     

Upper airways obstruction with bilateral vocal cord paralysis.

In ten patients with bilateral vocal cord paralysis, we demonstrated variable extrathoracic airway obstruction. The ratio of forced expiratory flow at 50 percent vital capacity to forced inspiratory flow at the same lung volume (VE50/VI50) was 1.65 +/- 0.77 (mean +/- 1 SD). There was marked variability of inspiratory flow obstruction with a mean VI50 of 1.63 +/- 0.75 liters/ sec and a range from 0.9 liters/sec to 3.2 liters/sec. Nine of the ten patients required tracheostomy for symptoms of dyspnea. Follow-up flow volume loops were obtained to document the effects of surgical intervention and tracheostomy.     

Oral terbutaline augments cardiac performance in chronic obstructive pulmonary disease

In previous research, we have demonstrated that parenterally administered terbutaline can augment resting cardiac function in patients with chronic obstructive pulmonary disease (COPD). Because the oral form of terbutaline is more widely utilized, a double-blind, randomized, crossover, placebo-controlled trial of the cardiopulmonary effects of oral terbutaline was conducted in ten patients with COPD. Right and left ventricular ejection fractions (RVEF and LVEF) were determined by first pass radionuclide angiography. There were no differences in spirometry and hemodynamic measurements between treatment and placebo days. Following 5 mg of oral terbutaline, there was a small but statistically significant increase in forced expiratory volume in 1 second and in heart rate, but no significant change in forced vital capacity or blood pressure. LVEF improved significantly with terbutaline both at rest (62% +/- 6% vs. 67% +/- 9%, mean +/- SD) and during submaximal steady state exercise (61% +/- 5% vs. 67% +/- 10%). RVEF improved significantly at rest (64% +/- 6% vs. 69% +/- 5%), but not during submaximal steady state exercise (65% +/- 6% vs. 68% +/- 7%). Thus, oral terbutaline produces significant improvement in biventricular systolic pump performance at rest, and increases left ventricular ejection fraction during submaximal exercise in patients with moderate to severe COPD.     

Relationship of constitutional factors and cigarette smoking to decrease in 1-second forced expiratory volume.

A 5-year prospective survey of 34 subjects with mild chronic bronchitis revealed marked individual variation in the annual rate of decrease in the forced expiratory volume in 1 sec. The mean annual decrease in the 1-sec forced expiratory volume was 0.046 +/- 0.057 liter. Although the annual decrease in the 1-sec forced expiratory volume was greater among smokers (0.056 +/- 0.061 liter per year) than non- and ex-smokers (0.016 +/- 0.021 liter per year; P less than 0.005), differences in tobacco consumption did not account for the individual variation. This variation was related, instead, to 3 phenomena believed to indicate the presence of host susceptibility to chronic bronchitis. These phenomena were bronchial reactivity to methacholine, ventilatory responsiveness to isoproterenol, and sputum eosinophilia. The correlation between the rate of decrease in 1-sec forced expiratory volume and the degree of methacholine reactivity was 0.76 (P less than 0.001); the correlation between the decrease in 1-sec forced expiratory volume and ventilatory responsoveness to isoproterenol was 0.45 (P less than 0.01). Deterioration of 1-sec forced expiratory volume was appreciably greater among those with sputum eosinophilia (0.062 +/- 0.06 liter per year) than among thse without eosinophilia (0.017 +/- 0.033 liter per year P less than 0.01). The progression of abnormality appeared to depend on an interaction between cigarette smoking and individual susceptibility. Even minimal tobacco consumption led to serious ventilatory deterioration when methacholine reactivity was high, whereas heavy smoking produced little effect on the decrease in 1-sec forced expiratory volume when methacholine reactivity was slight.     

Noninvasive ventilation during walking in patients with severe COPD: a randomised cross-over trial.

It was hypothesised that noninvasive positive-pressure ventilation (NPPV) applied during walking prevents exercise-induced hypoxaemia and improves exercise performance in severe chronic obstructive pulmonary disease (COPD) patients already receiving long-term NPPV. A total of 20 COPD patients (mean+/-sd age 65.1+/-8.7 yrs, forced expiratory volume in one second 27+/-8% predicted and total lung capacity 116+/-27% pred) reporting dyspnoea, even during mild exertion, underwent two 6-min walking tests with a rollator and supplemental oxygen (2.1+/-0.9 L.min(-1)) in a randomised cross-over design: with and without pressure-limited NPPV as used at home (inspiratory:expiratory pressure 2.9+/-0.44:0.4+/-0.1 kPa (29+/-4:4+/-1 mbar), respiratory frequency 20+/-2 breaths.min(-1)). The arterial oxygen tension significantly increased by 1.39+/-1.43 kPa (95% confidence interval (CI) 0.71-2.07 kPa) after walking with NPPV, but significantly decreased by 1.43+/-1.06 kPa (95% CI -1.92 - -0.94 kPa) without NPPV. Dyspnoea, as assessed by the Borg dyspnoea scale, significantly decreased from 6 (interquartile range (IQR) 4.5-10) to 4 (1.5-4.5) and walking distance significantly increased from 209 (IQR 178-279) to 252 (203-314) m when walking was NPPV-aided. In chronic hypercapnic chronic obstructive pulmonary disease, high-intensity noninvasive positive-pressure ventilation can also be administered during walking with unchanged ventilator settings compared with settings used at rest, thus resulting in improved oxygenation, decreased dyspnoea and increased walking distance. Therefore, noninvasive positive-pressure ventilation during walking could prevent hypoxia-induced complications and could, in future, play a role in palliative care.     

Determination of bronchodilation in the clinical pulmonary function laboratory. Role of changes in static lung volumes

Improved airway resistance following bronchodilator inhalation is not always accompanied by improvement in forced expiratory flow. We studied 241 patients with airways obstruction to learn whether changes in static lung volumes (vital capacity and function residual capacity measured by body plethysmography [FRCB]) would reveal bronchodilation not demonstrated by expiratory flow rates (the ratio of forced vital capacity at one second to the total forced vital capacity [FEV1/FVC]), and the forced expiratory flow for the midportion of the forced vital capacity (FEF25--75%). A significant fall in Raw occurred in 129 patients, 46 of whom had a significant increase in vital capacity (mean of + 465 ml +/- 43, P less than 0.001) and a fall in FRCB (mean of -763 ml +/- 78 P less than 0.001) with no change in FEV1/FVC% of FEF25--75%. We interpret these data to indicate that improvement in static lung volumes can reflect bronchodilation in the absence of improved expiratory flow.     

Mortality predictors in disabling chronic obstructive pulmonary disease in old age

OBJECTIVE: prospectively to evaluate predictors of mortality in elderly patients with disabling chronic obstructive pulmonary disease. METHODS: 137 (69 men) outpatients, aged 60-89 (mean 73) years with symptomatic disabling chronic obstructive pulmonary disease. We collected baseline demographic and physiological data. Subjects completed the Manchester Respiratory Activities of Daily Living Questionnaire, the Brief Assessment Schedule Depression Cards a screening questionnaire for depression, the Breathing Problems Questionnaire measuring quality of life, and the Montgomery Asberg Depression Rating Scale measuring severity of depression. All subjects were followed prospectively and survival and mortality data were confirmed by contacting general practitioners and scrutinising hospital notes at 30 months. RESULTS: the mean (standard deviation) of one second forced expiratory volume was 0.89 (0.3) litres. At 30 months, 44 patients (21 men, aged 61-89 [mean 75] years: 32% of the total) had died. Mean (standard deviation) baseline one second forced expiratory volume of those dying was 0.71 (0.2) litres. On logistic regression analysis, predictors of mortality were: Manchester Respiratory Activities Of Daily Living Questionnaire score (odds ratio=0.88, 95% confidence interval=0.80-0.97); pre-bronchodilator one second forced expiratory volume (odds ratio=0.04, confidence interval=0.005-0.32); body mass index (odds ratio=0.87, confidence interval=0.79-0.97); and long term oxygen therapy (odds ratio=3.17, confidence interval=1.04-8.36). Current smoking status, pack-years smoked, depression scores, quality of life scores, co-morbid diseases and social class did not predict mortality. CONCLUSION: disability, use of long-term oxygen therapy, pre-bronchodilator lung function and body-mass index were independent predictors of mortality in elderly patients with severe chronic obstructive pulmonary disease.     

Lung function after bilateral lower lobe lung volume reduction surgery for alpha1-antitrypsin emphysema.

This study explores the mechanism(s) of airflow limitation following lung volume reduction surgery (LVRS) in patients with emphysema due to homozygous alpha1-antitrypsin (AT) deficiency. Bilateral targeted lower lobe stapled LVRS using video thoracoscopy was performed in six patients (five males) aged 61+/-9 yrs (mean+/-SD) with alpha1-AT emphysema. Two patients received only a 6-month follow-up. However, four patients, at 22, 24, 27 and 36 months post-LVRS, noted relief from dyspnoea and increased walk tolerance. At 27+/-6 months (mean+/-SD) post-LVRS, their forced expiratory volume in one second improved only from 30+/-2% of the predicted value (mean+/-SEM) before surgery to 33+/-1% pred after surgery. Yet, total lung capacity (TLC) decreased from 151+/-13 to 127+/-10% pred; diffusing capacity increased from 35+/-9 to 59+/-9% pred; and vital capacity increased from 68+/-10 to 88+/-5% pred. In three patients, static lung elastic recoil at TLC increased from 1.1+/-0.15 to 1.2+/-0.10 kPa. Using flow/pressure curves, the mechanism for expiratory airflow limitation pre-LVRS and the improvement noted post-LVRS could be primarily accounted for by the initial loss and subsequent increase in lung elastic recoil. Bilateral lung volume reduction surgery provides modest physiologic improvement for 2-3 yrs in patients with alpha1-antitrypsin emphysema due to increases in lung elastic recoil.