Severe Chronic Airflow Obstruction Research Articles

Predictors of Survival in a Group of Patients with Chronic Airflow Obstruction

This article shows the results of a 10-year follow-up study conducted on a cohort of 870 patients affected by severe chronic airflow obstruction (CAO) on spirometric tests. The main aims of the study were to identify those factors associated with reduced survival in CAO patients and to evaluate the effectiveness of a care program on patients’ survival. The analysis compared the survival time and causes of death between patients who showed adherence and patients who did not show adherence to the care program. The most important results can be summarized as follows: (1) CAO patients have a high mortality rate for acute respiratory failure, cor-pulmonale, and lung cancer; (2) patient’s age at the time of selection to enter follow-up influences the death hazard; (3) patients who need long-term oxygen treatment (LTOT) have a higher death hazard than those who don’t need it; (4) the higher is FEV1 or PaO2 value at the time of selection, the lower the death hazard; (5) patients who need, and regularly take, long-term oxygen treatment have a lower death hazard compared to those who need it, but do not take it properly; and (6) patients with a partial reversible airway obstruction (pRAO) who regularly attend the clinic for planned check-ups, have a lower death hazard compared to those who have the same characteristics, but do not show adherence to the care program. These results indicate that an organized program to treat severe CAO patients may improve their survival.

Pressure support reduces inspiratory effort and dyspnea during exercise in chronic airflow obstruction.

Exercise training has been of limited success in patients with severe chronic airflow obstruction (CAO), in part because of the reduced ventilatory capacity and excessive dyspnea experienced. Pressure support (PS) is a new form of mechanical ventilation which can effectively assist ventilation when applied noninvasively to patients in acute respiratory failure. It was hypothesized that PS might also be used to improve exercise performance, and ultimately physical conditioning, in ambulatory patients with CAO undergoing exercise training. To begin to address this concept, the objectives of the present study were (1) to examine the feasibility of providing PS to exercising patients with CAO and (2) to determine its effects on breathing pattern, inspiratory effort, and dyspnea. Flow and volume, mouth, esophageal, and gastric pressure were measured in seven patients with severe CAO (mean FEV1 = 0.75 +/- SEM 0.09 L) performing constant workload bicycle exercise (33 +/- 6 watts) during control conditions and with the application of PS (approximately 10 cm H2O). PS increased minute ventilation as a result of changes in both tidal volume and respiratory rate. This occurred despite marked reductions in inspiratory effort, as indicated by the pressure-time integrals of esophageal (68 +/- 5% control, p < 0.0005) and transdiaphragmatic pressure (52 +/- 8% control, p < 0.0005). Using a 5-point bidirectional scale to assess changes in dyspnea, breathlessness improved significantly with the addition of PS (2.3 +/- 0.6, p < 0.05) and worsened to a similar degree when it was removed (2.1 +/- 0.5, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Pressure support reduces inspiratory effort and dyspnea during exercise in chronic airflow obstruction.

Exercise training has been of limited success in patients with severe chronic airflow obstruction (CAO), in part because of the reduced ventilatory capacity and excessive dyspnea experienced. Pressure support (PS) is a new form of mechanical ventilation which can effectively assist ventilation when applied noninvasively to patients in acute respiratory failure. It was hypothesized that PS might also be used to improve exercise performance, and ultimately physical conditioning, in ambulatory patients with CAO undergoing exercise training. To begin to address this concept, the objectives of the present study were (1) to examine the feasibility of providing PS to exercising patients with CAO and (2) to determine its effects on breathing pattern, inspiratory effort, and dyspnea. Flow and volume, mouth, esophageal, and gastric pressure were measured in seven patients with severe CAO (mean FEV 1 =0.75±SEM 0.09 L) performing constant work-load bicycle exercise (33±6 watts) during control conditions and with the application of PS (approximately 10 cm H 2 O). PS increased minute ventilation as a result of changes in both tidal volume and respiratory rate. This occurred despite marked reductions in inspiratory effort, as indicated by the pressure-time integrals of esophageal (68±5% control, p<0.0005) and transdiaphragmatic pressure (52±8% control, p<0.0005). Using a S-point bidirectional scaIe to assess changes in dyspnea, breathlessness improved significantly with the addition of PS (2.3±0.6, p<0.05) and worsened to a similar degree when it was removed (2.1±0.5, p<0.05). In conclusion, PS was well tolerated in exercising patients with severe CAO and effectively assisted ventilation, reducing both inspiratory effort and dyspnea. These results indicate that further work is warranted to determine whether PS can facilitate exercise reconditioning and improve physical fitness in patients enrolled in an exercise training program

Responsiveness and variability of airflow obstruction in chronic obstructive pulmonary disease. Clinicopathologic correlative studies.

We have studied the relationships between pulmonary lesions and bronchodilator response and variability of FEV1 in 41 patients enrolled in the National Institutes of Health Intermittent Positive Pressure Breathing Trial who died, came to autopsy, and provided adequate tissue to quantitate lesions. The patients had moderate to severe chronic airflow obstruction and various degrees of response to 250 micrograms isoproterenol inhalation. Airway responsiveness was positively correlated with bronchial eosinophilia, bronchial inflammation, and bronchiolar fibrosis, and it was negatively correlated with bronchiolar goblet cell metaplasia and emphysema. Patients with an increase of 190 ml or more in FEV1 after bronchodilator had less bronchial cartilage and less goblet metaplasia in bronchioles. Airway smooth muscle was not related to airway responsiveness and variability. Flow rates were adversely affected by bronchial eosinophilia for given emphysema scores. This study shows the importance of the eosinophil as part of chronic nonspecific lung disease. Lack of airway responsiveness was associated with lesions such as emphysema and goblet cell metaplasia, which by themselves cause severe chronic airflow obstruction. The better-preserved lung function in patients with increased airway responsiveness is attributed to negative correlations with emphysema and positive correlations with bronchial eosinophilia.

Responsiveness and Variability of Airflow Obstruction in Chronic Obstructive Pulmonary Disease: Clinicopathologic Correlative Studies

We have studied the relationships between pulmonary lesions and bronchodilator response and variability of FEV1 in 41 patients enrolled in the National Institutes of Health Intermittent Positive Pressure Breathing Trial who died, came to autopsy, and provided adequate tissue to quantitate lesions. The patients had moderate to severe chronic airflow obstruction and various degrees of response to 250 micrograms isoproterenol inhalation. Airway responsiveness was positively correlated with bronchial eosinophilia, bronchial inflammation, and bronchiolar fibrosis, and it was negatively correlated with bronchiolar goblet cell metaplasia and emphysema. Patients with an increase of 190 ml or more in FEV1 after bronchodilator had less bronchial cartilage and less goblet metaplasia in bronchioles. Airway smooth muscle was not related to airway responsiveness and variability. Flow rates were adversely affected by bronchial eosinophilia for given emphysema scores. This study shows the importance of the eosinophil as part of chronic nonspecific lung disease. Lack of airway responsiveness was associated with lesions such as emphysema and goblet cell metaplasia, which by themselves cause severe chronic airflow obstruction. The better-preserved lung function in patients with increased airway responsiveness is attributed to negative correlations with emphysema and positive correlations with bronchial eosinophilia.

Neck muscle activity in patients with severe chronic obstructive pulmonary disease.

The present studies were designed to assess the pattern of activity and the frequency of activation of the neck muscles in patients with chronic obstructive pulmonary disease (COPD). Using concentric needle electrodes, we thus recorded the electromyograms of the scalene, sternocleidomastoid, and trapezius muscles during resting breathing in 40 stable patients with severe chronic airflow obstruction (FEV1 = 0.69 +/- 0.18 L) and hyperinflation (FRC = 228 +/- 40% of predicted); 17 patients were hypercapnic at rest. When breathing in the seated posture, all patients (100%) had strong inspiratory contraction of the scalenes. In contrast, no patient showed inspiratory activity in the trapezius, and only four patients (10%) showed definite, invariable inspiratory activity in the sternocleidomastoid. These two muscles were silent in the supine posture as well, even though the adoption of this posture was associated with an increase in dyspnea in most patients. We conclude, therefore, that in contrast to conventional thinking, most stable patients with severe COPD do not use the sternocleidomastoids or the trapezii when breathing at rest. Additional measurements indicated that the sternocleidomastoid inspiratory activity previously recorded in such patients was in general caused by a cross-contamination from surrounding muscles.

Effect of High-Dose Salbutamol on Cardiac Rhythm in Severe Chronic Airflow Obstruction: A Controlled Study

Despite concern over possible adverse cardiac effects of high-dose beta-agonists there have been no controlled studies of the effects of such a therapy in patients with severe chronic airflow obstruction (CAO). We therefore studied 22 CAO patients (FEV < 1 litre) with continuous ambulatory cardiac monitoring. Patients received either nebulised salbutamol (5 mg) or saline each given 4 times daily for 24 h on 2 consecutive days, single blind, in random order. Supraventricular arrhythmias were common on both saline and salbutamol days (8 vs. 9 patients, p = NS), but none were clinically apparent. There were no episodes of ventricular tachycardia. Ventricular ectopic activity was highly variable but did not significantly differ between the two study days overall or between specific periods after nebulised salbutamol or saline. Serum potassium (mean) fell by 0.23 (SD 0.06) mmol/l in 10 patients after salbutamol. Baseline FEV1, PaO2, PCO2 were not predictive of arrhythmias or ectopic activity. While occasional adverse effects cannot be excluded, we conclude that high-dose salbutamol does not lead to any general increase in arrhythmogenic potential in severe CAO.

Supported Arm Exercise vs Unsupported Arm Exercise in the Rehabilitation of Patients With Severe Chronic Airflow Obstruction

Compare unsupported (UAEx) vs supported (SAEx) arm exercise in training of patients with severe chronic airflow obstruction (CAO). Randomized trial of UAEx vs SAEx training added to a 10-week outpatient program of lower extremity (LE) exercise training, respiratory muscle training, breathing retraining, psychological support, and teaching. The Lahey Clinic Medical Center, a tertiary referral center. Forty patients with CAO entered the rehabilitation program with 32 completing training and testing. All underwent progressive bicycle ergometer and treadmill training and respiratory muscle training using a threshold inspiratory pressure trainer. Patients were randomized to progressive SAEx training (arm cycle ergometer, n = 17) or UAEx training (raising weighted dowel, n = 18). There was no significant difference in disease severity or exercise capacity between the two groups. Twelve-min walk test, bicycle ergometer power output, and respiratory muscle function improved with no significant difference in improvement between the two groups. Both groups showed similar improvements in arm ergometer testing while those trained with UAEx showed greater improvement in dowel testing (UAEx > SAEx, p = 0.002). In 17 patients VO2isotime (time at which patient performed pre-training and post-training tests) was measured during dowel testing. Only those trained with UAEx showed decreases in VO2isotime (UAEx trained, p = 0.02; SAEx, p = 0.18). VO2 during the last minute of a 2-min period of simple arm elevation was also measured in 17 patients. Only those trained with UAEx showed decreases in VO2 (UAEx, p = 0.02; SAEx, p = 0.20). We confirm that a pulmonary rehabilitation program incorporating exercise training improves LE and respiratory muscle function. Arm exercise training improved arm activity with greater increases in unsupported arm activity seen in those trained with unsupported arm training. Metabolic cost of UAEx decreased only in those trained with UAEx. As UAEx is typical of activities of daily living in patients with CAO, the changes seen with UAEx training may be of greater clinical significance. Arm training should be incorporated in exercise training and a simple program of UAEx appears the optimal format.

Regional structure-function correlations in chronic obstructive lung disease measured with positron emission tomography.

Positron emission tomography, performed with isotopes of very short half life, can be used to relate local lung tissue density to local ventilation and to the ventilation:perfusion ratio. This method has been used in 10 patients with severe chronic airflow obstruction and differing values for carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO). Ventilation (VA) and the ventilation:perfusion ratio (V/Q), lung density, and blood volume were measured regionally in a single transaxial section at mid-heart level with the patients in a supine position. Alveolar volume, extravascular tissue lung density, and perfusion (Q) were derived. Twenty five regions with abnormalities in the ventilation images were analysed. Tissue density showed a negative correlation with the ratio V/Q (r = 0.55) and a positive correlation with Q (r = 0.59) and blood volume (r = 0.65). In four patients with a low carbon monoxide transfer factor (TLCO) and transfer coefficient (KCO) < 50% predicted many regions with low VA had low tissue density and normal or high V/Q. On the other hand, in four patients with TLCO and KCO > 50% predicted many regions with low VA had normal or high tissue density and low values of V/Q. The other two patients had patterns between these two extremes. Individual ratios between mean values of tissue density and V/Q had a positive correlation with KCO (% pred; r = 0.79). These findings link structural differences with distinctive functional patterns; they reinforce the view that bronchial inflammation or oedema predominate in some patients with chronic airflow obstruction, whereas alveolar destruction is the major feature in others.

Abdominal muscle use during breathing in patients with chronic airflow obstruction.

To assess the pattern of abdominal muscle contraction in stable patients with chronic obstructive pulmonary disease (COPD), we studied electromyograms of the rectus abdominis, external oblique, and transversus abdominis muscles in 40 patients with variable degrees of chronic airflow obstruction (FEV1 between 17 and 82% of predicted); 12 control subjects with normal pulmonary function tests were studied for comparison. The subjects were studied during resting breathing in the supine posture, and the electromyograms were recorded with concentric needle electrodes implanted with the aid of a high-resolution ultrasound. The rectus abdominis and external oblique were silent in virtually all patients. In contrast, 17 patients had invariable phasic expiratory activity in the transversus abdominis, and 11 additional patients had intermittent transversus expiratory activity. Expiratory contraction of the transversus was related to the degree of airflow obstruction (p less than 0.005), and when present, it persisted in the seated posture. We conclude that (1) when breathing at rest, many stable patients with severe chronic airflow obstruction contract the abdominal muscles during expiration, and (2) this expiratory contraction is usually confined to the transversus muscle. These observations also indicate that the physiology of dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP) in such patients should be reevaluated.

Transpulmonary angiotensin II formation and pulmonary haemodynamics in stable hypoxic lung disease: the effect of captopril

The effect of chronic hypoxic lung disease on the activity of the renin-angiotensin (RA) system and the role the RA system plays in the pulmonary vascular changes that accompany hypoxia remain controversial. We have measured transpulmonary generation of angiotensin II (A II) and pulmonary haemodynamics in nine patients with airflow obstruction (mean FEV1 = 0.741) and arterial hypoxaemia (mean PaO2 = 8.4 Pa) before and after captopril. In each patient pulmonary artery pressure, cardiac output, systemic arterial pressure, arterial and mixed venous blood gas tensions and arterial and mixed venous A II were measured at rest and at intervals for a total of 3 h after 25 mg captopril orally. The patients had moderate pulmonary hypertension (mean = 29 mmHg) and slightly raised A II levels (mean = 47.2 pg ml-1) but no step-up in A II levels across the lung. After captopril, both arterial and mixed venous A II levels fell by, on average 80% (SEM 2%), but the transpulmonary gradient for A II remained unchanged for each subject. The systemic arterial pressure fell by an average 18% (SEM 5%). In seven patients pulmonary vascular resistance fell (mean = 31%, SEM 6%) and in two patients it rose. There was no significant change in blood gas tensions. These findings suggest that patients with chronic hypoxic lung disease have decreased conversion of A I to A II in the lung but stimulation of the extra-pulmonary renin-angiotensin system. ACE inhibition appears to cause a fall in PVR in most patients with severe chronic airflow obstruction without deterioration in gas exchange.

Alveolar Attachments in Emphysema of Human Lungs

We have studied alveolar attachments to membranous bronchioles in 41 patients enrolled in the National Institutes of Health Intermittent Positive Pressure Breathing Trial who died, came to autopsy, and provided adequate tissue for examination. The patients had moderate to severe chronic airflow obstruction and, on the average, severe emphysema. We measured the number of normal attachments per membranous bronchiole per case (N), the number of normal attachments per mm of circumference per bronchiole per case (Nunit), and the ratio of abnormal to all attachments (R). All measurements correlated closely to all measurements of emphysema and to irregular shape of bronchioles (deformity index). Measurement of abnormal attachments correlated with abnormal tests of pulmonary function, including evidence of airflow obstruction and diffusing capacity for carbon monoxide (DLCO). Nunit showed the most frequent correlations, but both N and Nunit were only related independently of emphysema for Phase III of the single-breath nitrogen test. R was related to loss of DLCO. We conclude that loss of attachments is not itself a cause of airflow obstruction but rather a correlate of emphysema, which is the proximate cause of the obstruction. Loss of alveolar attachments has an effect only on the single-breath nitrogen tests independent of emphysema.

Oral diamorphine: lack of effect on dyspnoea and exercise tolerance in the "pink puffer" syndrome

The aim of this study was to assess the effects of diamorphine on breathlessness and exercise tolerance in patients with severe chronic airflow obstruction and normal arterial carbon dioxide tension (PCO2) levels ("pink puffer" syndrome). In this double-blind, cross-over, randomized study we examined both acute and chronic effects of single and multiple doses of oral diamorphine in 14 "pink puffer" patients. Their mean resting forced expiratory volume in one second (FEV1) was 36% predicted normal, mean arterial oxygen tension (PaO2) was 9.2 kPa and mean PaCO2 was 5.2 kPa. Ten patients took either diamorphine 2.5 or 5 mg or placebo elixir 6 hourly for 2 weeks, recording on a diary card dyspnoea, sleepiness and well-being on a visual analogue scale (VAS). The final treatment was given 30 min before measuring spirometry, arterial blood gases, plasma morphine levels, 6 min walking distances, time walked on treadmill and self-assessment of dyspnoea on a VAS scale after exercise. On two further days, eight patients took two doses, 4 h apart, of either diamorphine 7.5 mg or placebo elixir. Spirometry, 6 min walking distance with a VAS score for dyspnoea were measured before and at 1 h after each dose. Morphine levels and blood gases were also measured. Whether given in single or repeated doses, oral diamorphine had no significant effect on exercise tolerance and breathlessness when compared with placebo. Diamorphine 2.5-7.5 mg produced neither sleepiness nor a deterioration in blood gases. However, plasma levels associated with analgesic efficacy were not achieved with these doses. Thus, as given in this study, oral diamorphine is unlikely to have therapeutic potential in the treatment of dyspnoea in the "pink puffer" syndrome.

Breathing muscle activity during expiration in patients with chronic airflow obstruction

During quiet ventilation in 10 patients with severe chronic airflow obstruction (AFO) there were large tidal swings of pleural pressure, 15.8 +/- 5.1 cmH2O, with high negative pressures achieved, 15.2 +/- 5.2 cmH2O. The pattern of pleural pressure mirrored that of tidal expiratory flow with a rapid rise to maximum of pleural pressure and flow at the beginning of expiration, a slow decline of both throughout most of expiration, and just before the onset of inspiration at flow reversal, a sharp fall in pleural pressure and expiratory flow. The shape of expiratory flow and pleural pressure tracings and the pattern of EMG recordings are compatible with loss of post-inspiratory muscle braking of flow. The generally negative pleural pressure and the EMG silence during expiration indicated relaxation of expiratory muscles throughout expiration. Extrapolation of the tidal expiratory flow curve to zero, and calculation of the area under the extrapolated curve showed the volume of dynamic hyperinflation to be a small proportion of the total increase in functional residual capacity above the predicted value in these patients.

Pathology of Chronic Airflow Obstruction

Classification of chronic airflow obstruction may be based on the site of the obstructing lesions. It is seldom that only one type of lesion is present, but one may often dominate. In chronic bronchitis, the major disease of large airways, chronic mucus hypersecretion, is reflected by an increase in size of bronchial mucous glands. This may be a factor in airway narrowing, especially with coexisting edema of the airway wall. Excess intralumenal mucus compounds the obstruction. Increased airways reactivity is present in 15 to 70 percent of patients with chronic airflow obstruction. Increased airway muscle and cartilage atrophy are features of chronic bronchitis, but the association of increased muscle with increased airway reactivity is poor. Inflammation of the small airways (bronchiolitis) is a significant complication for cigarette smokers and is an important cause of mild chronic airflow obstruction. Goblet cell metaplasia is a reflection of chronic small airways inflammation and, together with intralumenal mucus, is an important feature. Permanent narrowing of the small airways presumably results from inflammation with consequent fibrosis, while functional narrowing results from release of mediators of inflammation. Increased muscle mass is present in some cases. Distortion and irregularity of small airways related to emphysema are major factors in severe obstruction. Lesser degrees of emphysema may be associated with a diminished number of alveolar attachments and mild chronic airflow obstruction. Emphysema, the dominant lesion in patients with severe chronic airflow obstruction, results from parenchymal lesions. Centrilobular emphysema, in which the respiratory bronchioles are selectively or dominantly involved, is the most common form.(ABSTRACT TRUNCATED AT 250 WORDS)

Paying the piper — the linkage of alveolar ventilation to alveolar pressure

The most basic aspects of positive pressure ventilation are generally well appreciated by modern practitioners of critical care. Yet, even after decades of application, many nuances of mechanical ventilation (MV) are incompletely understood. In this issue of Intensive Care Medicine, Conti et al. [1] have provided convincing evidence that rethinking and additional research are needed to consolidate our understanding. In studying a sample of patients with severe chronic airflow obstruction, these authors demonstrated that high-frequency jet ventilation (HFJV) at 120 breaths per minute produced similar levels of end-expiratory alveolar pressure (auto-PEEP) to those yielded by conventiona] MV accomplishing similar CO 2 elimination. In view of the apparent simplicity of MV, it is interesting to note that this work is based on two concepts high frequency ventilation (HFV) and autoPEEP that were essentially unknown or unrecognized by the medical practitioner of 10 years ago. In clinical practice, three forms of ventilation are in widespread use: conventional (volume-cycled) ventilation, pressure-preset ventilation (PPV), and HFJV. Clinicians tend to have a good intuitive sense regarding volume-cycled ventilation, understanding that this mode guarantees the ventilation that occurs per unit time, but at the cost of raising alveolar pressure. Pressure-preset ventilation (pressure support, pressure control, inverse ratio, airway pressure release) and HFJV are less intuitive and less well understood. Yet a firm understanding of their ventilatory characteristics is crucial to scientific management. Perhaps no aspect of MV engenders quite as much confusion and uncertainty as high-frequency ventilation. The flurry of interest in HFV that began about 1980 peaked mid-decade, spurred by the recognition that effective gas exchange could be maintained by machines that rapidly cycle with a tidal volume smaller than the calculated anatomical deadspace. As investigators explored this phenomenon, exotic mechanisms to supplement convection were suggested to account for effective alveolar ventilation and gas transfer. Most such mechanisms, however, apply only at very high cycling frequencies. During HFJV at rates of 100-200/min (a range incorporating the frequency studied by Conti), the primary mechanism of alveolar ventilation is likely to be that of bulk (convective) flow [2]. It is important to know this fact, because as long as convective mechanisms prevail, the relationship of alveolar pressure to alveolar ventilation is both intimate and predictable. The parallel between HFJV and pressure-preset ventilation at conventional rates may not be obvious, but it is well worth considering. When HFJV is applied to the airway, approximately square waves of airway pressure (similar in form to those of PPV) are generated a short distance downstream of the injector and, as already noted, the primary mechanism of alveolar ventilation is convective for both modes. In a real sense, therefore, HFJV applied at moderate frequencies (~100/min) closely resembles PPV with small tidal volumes. The similarities extend further. In both HFJV and PPV, the clinician selects a fixed pressure with which to work, and once this is chosen, the clinician varies only two other parameters the inspiratory time fraction ( t i / t t o t ) and the cycling frequency. The other crucial determinants of alveolar ventilation and alveolar pressure (the key outcome variables of the ventilatory process) are a function of the patient's impedance to volume change the elastance of the respiratory system (the reciprocal of compliance) and airflow resistance. As cycling frequency increases at a fixed ti/ttot, the durations of inspiration and expiration progressively shorten. However, assuming that total alveolar ventilation (~ralv) remains the same and that purely convective mechanisms apply, the average rates of expiratory and inspiratoy flow are in-

Comparison of Outpatient Nebulized vs Metered Dose Inhaler Terbutaline in Chronic Airflow Obstruction

Eighteen patients (nine asthmatic patients and nine with poorly reversible airflow obstruction) with stable, severe chronic airflow obstruction, completed a four-week randomized, doubled-blind, placebo-control, crossover trial comparing the acute and chronic effects of terbutaline administered by metered-dose inhaler (MDI) and nebulizer (NEB). Equipotent doses of terbutaline were selected from the comparison of separate cumulative dose-response curves for MDI and NEB. The MDI and NEB given acutely produced similar bronchodilatation and improvement in exercise performance. Spirometric indices, 6 min walking distance, symptom scores and extra beta-agonist use were no different between MDI and NEB treatment fortnights in the outpatient study. We conclude that the degree of bronchodilatation achieved in these patients is a reflection of the dose of bronchodilator administered and not the mode of administration. There is no justification for the preferred outpatient use of nebulized bronchodilators in patients with stable chronic airflow obstruction who can use adequate doses of bronchodilators via a metered-dose inhaler.

Prognosis of chronic obstructive pulmonary disease: the Dutch experience.

This article summarizes the Dutch experience with prognosis in three groups of patient with chronic obstructive pulmonary disease. (1) 129 patients with severe chronic airflow obstruction (mean FEV1 1,880 ml, range 1,200 to 2,500 ml); (3) 81 patients out of group 2 with decline in FEV1 over time, without oral corticosteroids. It is clear that, at least in the presence of regular therapy, next to cessation of smoking, a higher reversibility of airflow obstruction and lower degree of airway hyperreactivity are important predictors of a slower decline in FEV1. In our opinion these findings point to the urgency for clinicians to change the nihilistic attitude towards patients with CAO, in that both smoking cessation and an early therapy directed at the reversible part of airflow obstruction and airway hyperreactivity may be able to prevent deterioration. Future studies have to show whether long-term, ongoing therapy with corticosteroids may even change the progression and survival in far advanced disease.

The National Institutes of Health Intermittent Positive-Pressure Breathing Trial: pathology studies. IV. The Destructive index.

A Destructive Index (DI) was recently devised by Saetta and coworkers (7), and their data suggest that the DI may be a better assessment of emphysema than the traditional indexes. We have applied the DI as well as conventional assessments of emphysema-panel grading (emphysema score), mean linear intercept (Lm), and internal surface area at a volume of 5 L (ISA5) - to the lungs of patients in the National Institutes of Health Intermittent Positive Pressure Breathing Trial, which admitted patients with moderate to severe chronic airflow obstruction. In the 41 patients with satisfactory morphologic material who died and were autopsied, the DI was significantly correlated with emphysema score (p less than 0.001), Lm (p less than 0.001), and ISA5 (p less than 0.001). There was a rapid increase in the DI between emphysema scores of 30 and 60; when the DI reached a score of about 90, it did not increase much further. A wide spread of the DI from 23.7 to 86.5 was present in lungs with a Lm of less than 0.55 mm. The DI was well related to the diffusing capacity for carbon monoxide (DLCO) (p less than 0.001) and %TLC (p less than 0.01), but not to %FEV1, slope of phase III (phase III), nor recoil pressure at 90% of TLC (P90). The correlations between emphysema score and either DLCO or %TLC were about the same as for the DI. Also, correlations were significant for %FEV1, phase III, and P90. Lesions of bronchioles had no correlation with the DI. We therefore conclude that the DI is related to conventional assessments of emphysema, but beyond an emphysema score of 55 or a Lm of 0.55 mm, it does not discriminate emphysema severity.(ABSTRACT TRUNCATED AT 250 WORDS)

High dose salbutamol in chronic airflow obstruction: comparison of nebulizer with Rotacaps

Patients with severe chronic airways obstruction often respond poorly to inhaled salbutamol in conventional dosage from a pressurized aerosol. We have investigated the response to high dose salbutamol in 18 patients with chronic airways obstruction (mean age 64.4 years, mean FEV1 40.2% predicted, less than 15% response to 400 micrograms salbutamol). Patients were given 1 mg, 2 mg and 5 mg of salbutamol by either Rotacaps or nebulizer in random order on separate days. Response was measured over 8 h as a change in airway calibre (FEV1, FVC and PEF). The frequency of tremor, palpitations and arrhythmias was noted. Area under the curve for change from baseline values for FEV1, FVC and PEF showed that larger doses of salbutamol (nebulized or Rotacaps) result in larger areas from all three variables. Analysis of peak response, for FEV1, FVC and PEF showed no significant difference for the six treatments used except that the peak response for 2 mg Rotacaps for FEV1 was significantly larger than that for 1 mg Rotacaps (P less than 0.05). The results of this study show that in severe chronic airflow obstruction 1, 2 and 5 mg of salbutamol inhaled via a rotahaler device are just as effective as 1, 2 and 5 mg salbutamol inhaled from a nebulizer in producing bronchodilation. High dose salbutamol is well tolerated and side effects are minimal. Rotacaps have the advantage of being more portable than a wet nebulizer.