Mild Hypoxemia Research Articles

Effect of Prazosin on Hypoxemia-Induced Blood Flow Redistribution in the Newborn Piglet

We examined the effect of the alpha 1-adrenergic antagonist prazosin on blood pressure, left ventricular output and blood flow redistribution during normoxemia and mild hypoxemia in the chronically instrumented, unanesthetized newborn piglet employing the radiolabeled microsphere technique. Prior to prazosin, hypoxemia caused increases in aortic pressure and blood flows to the brain, myocardium and diaphragm, accomplished by small, statistically insignificant decreases in flows to the carcass and viscera without an increase in cardiac index. Prazosin treatment during normoxemia caused a fall in blood pressure and resulted in greater blood flows of left ventricular origin to the carcass, myocardium and lung. Hypoxemia after prazosin administration increased not only aortic pressure and blood flows to the brain, myocardium and diaphragm, but also, unlike the situation before drug treatment, cardiac index. Thus, in the newborn piglet, the maintenance of critical organ oxygen delivery during hypoxemia is not blocked by prazosin, but is accomplished by an increase in cardiac index rather than simply by redistribution of blood flow.

Fetal swallowing: response to graded maternal hypoxemia

A computer-based system, incorporating electromyography (EMG) and esophageal fluid flow measurement, was used to determine fetal breathing and swallowing responses to graded maternal hypoxemia. Five chronically prepared ewes with singleton fetuses at a gestational age of 130 +/- 2 (SE) days were subjected to successive 30-min periods of mild and moderate hypoxemia (inspired O2 fraction = 0.16 and 0.13, respectively). Mild and moderate maternal hypoxemia evoked significant reductions in fetal arterial PO2 (21 +/- 1 to 17 +/- 1 and 13 +/- 1 Torr, respectively), while fetal arterial pH, hematocrit, plasma osmolality, heart rate, and mean blood pressure did not change. Moderate hypoxemia was associated with significant increases in fetal plasma arginine vasopressin and renin activity and significant reductions from basal values in percent time breathing (53 +/- 4 to 25 +/- 12%), percent time swallowing (11.5 +/- 3.1 to 1.3 +/- 0.7%), and volume swallowed (21.3 +/- 2.1 to 4.8 +/- 2.7 ml/30 min). Fetal swallowing activity was better correlated with arterial PO2 (r = 0.8) than breathing activity (r = 0.45). We conclude that fetal swallowing is suppressed during mild and moderate hypoxemia. It is suggested that several sites and/or mechanisms may account for the hypoxemic inhibition of fetal activities.

EVALUATION OF EQUTTHESIN AS A GENERAL ANAESTHETIC IN CAMELS (Camelus dro-medarius)

Summary The effects of equithesin administered IV “to effect” were evaluated in twelve adult domesticated camels (Camelus Dromedarius). The mean dose required for “to effect” anaesthesia as 0.74 ± 0.03 ml/kg. Moderate relaxation of muscles lasted 30 to 45 minutes and duration of analgesia was 10–15 minutes. The sleeping time was 15 to 45 minutes and the animals showed recovery in 75–115 minutes. During anaesthesia, there was moderate tachycardia, transient hypotension and decrease in central venous pressure. Primary T wave changes were a consistent finding in the ECG. There was mild hypoxemia, mild hypercapnia and significant decrease in arterial-venous oxygen tension difference. A significant decrease in the total leucocyte count occurred during the peak effect of anaesthesia. Hyperglycaemia observed at the peak anaesthetic effect was followed by hypoglycaemia 24 hours after administration of equithesin. The changes in rectal temperature, respiratory rate and other biochemical constituents studies were not significantly affected.

HYPOXAEMIA DURING ANAESTHESIA—AN OBSERVER STUDY

We have investigated 296 inpatients in a single-blind observer study to determine the incidence, degree and duration of hypoxaemia during anaesthesia. The clinical recognition of hypoxaemia, period of time until recognition and risk factors were studied. Oxygen saturation (Spo2) was monitored continuously with a pulse oximeter (Ohmeda, model 3700). One or more episodes of mild hypoxaemia (Spo2 86-90%) were recorded in 53% of patients. Severe hypoxaemia with Spo2 values less than 81% were recorded in 20% of patients. The mild hypoxaemic episodes lasted up to 34.6 min (mean 2.3 min) and 70% were not detected by the anaesthetist. In the remaining 30% of episodes, the anaesthetist diagnosed the complication with a mean time delay of 70 s. After intervention a mean time delay of 57 s was recorded until Spo2 exceeded 90%. Utilizing a stepwise multiple logistic regression analysis, we found that risk factors associated with a greater incidence of hypoxaemia were patient age (P less than 0.005) and anaesthetic technique (P less than 0.00001). We conclude that hypoxaemic episodes in our operating rooms are common during anaesthesia and suggest preoxygenation in all patients in addition to administration of supplementary oxygen during arousal from anaesthesia and during transfer to the recovery room.

Pro: Nitrous oxide should not be used in patients with coronary artery disease

T IS REMARKABLE that an agent that cannot produce complete anesthesia under normal conditions and has a long list of serious adverse effects, continues to be used during millions of surgical and dental procedures annually. It has been suggested that if this gas were now presented to the Food and Drug Administration as a new drug, it most likely would not be approved.’ The long history of nitrous oxide use does not in itself justify its continued popularity. This agent gained acceptance when there were few safe alternatives and only the robust could expect to survive an anesthetic. Today, the ability to detect adverse consequences of anesthesia has improved and patients are less accepting of any anesthesia-related morbidity. Even the highly desirable pharmacokinetic properties of N,O are now challenged by new intravenous agents, and in the near future wil1 be matched by new rapidly eliminated volatile agents. The following, more objective, portion of this essay wil1 focus on the effects of nitrous oxide on the cardiovascular system, but indirect consequences must be considered as well. Postoperative nausea and vomiting, mild hypoxemia, or injuries due to the transfer of nitrous oxide to closed gas spaces, although rarely of serious consequente in a healthy patient, may dangerously stress a patient with coronary artery disease (CAD).

Hormonal and biophysical responses to acute hypoxemia in fetal sheep at 0.7–0.8 gestation

We examined whether there was a minimal change in fetal arterial Po2 necessary to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol or to affect the incidence of breathing movements or eye movements in fetal sheep at 106-117 days of gestation. Fetal sheep were exposed to two levels of hypoxemia, mild (4.1 mmHg Po2 drop) (1 mmHg = 133.32 Pa) and moderate (8.4 mmHg Po2 drop), for 1 h without acidemia. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia. In moderate hypoxemia, there were significant increases of fetal adrenocorticotropic hormone and arginine vasopressin and decreased incidence of fetal breathing movements. However, there were no significant changes in cortisol or eye movements. We conclude that a fetal arterial Po2 drop of between 4.1 and 8.4 mmHg is necessary to elicit responses to hypoxemia in fetal sheep at 106-117 days of gestation in adrenocorticotropic hormone, arginine vasopressin, and fetal breathing movements, but this degree of hypoxemia does not cause changes in cortisol or fetal eye movements.

Severe Hypoxemia and Liver Disease

Severe hypoxemia and orthodeoxia in patients with chronic liver disease is uncommon, but, when present, it is incapacitating. The purpose of this study was to determine the distribution of alveolar ventilation-perfusion (A/) in six patients with mild liver disease and severe hypoxemia (PaO2 at rest in sitting or standing position ranged from 35 to 67 mm Hg). Orthodeoxia was documented with improvement in Pao2 in the supine position in each patient (PaO2 at rest in supine position ranged from 46 to 75 mm Hg). A/ distribution was measured by the multiple inert gas elimination technique. The dispersion of A/ was increased with small portions of the cardiac output (0.5 to 14.8%) perfusing low A/ areas (O < A/ < 0.1). Another major finding was a large right-to-left shunt (A/ < 0.005) that ranged from 4 to 28%. The A/ mismatching and the right-to-left shunt both contributed to the hypoxemia. The predicted PaO2 was 5.5 mm Hg (p < 0.01) larger than the measured PaO2. In each patient, the mean pulmonary artery pre...

Polyneuropathy associated with chronic hypoxaemia: prevalence in patients with chronic obstructive pulmonary disease

The prevalence of clinical and electrophysiological signs of peripheral nerve disease was evaluated in 151 patients with chronic obstructive pulmonary disease. Patients with concomitant disorders affecting the peripheral nervous system were excluded. Thirty patients had clinical signs of a mild sensorimotor and distal neuropathy and 13 additional patients had only electrophysiological abnormalities. The rate and the severity of the neuropathy correlated with the severity of chronic hypoxaemia. Three out of 20 patients with mild hypoxaemia (PaO2 less than 15 mm Hg below normal) had polyneuropathy as compared with 15 out of 36 with severe hypoxaemia (PaO2 more than 30 mm Hg below normal (rates different at the 10% level)). PaO2 and age were the only variables discriminating between patients with and without peripheral neuropathy.

Threshold of hormonal and biophysical responses to acute hypoxemia in fetal sheep at different gestational ages

We examined whether there was a threshold for change in fetal arterial PO2 to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol, or to affect the incidence of fetal breathing movements or eye movements and we determined whether such a threshold changed with gestational age. Fetal sheep were exposed to two levels of hypoxemia, mild (4.6-5.3 mmHg PO2 drop) and moderate (8.3-8.8 mmHg PO2 drop) (1 mmHg = 133.322 Pa) for 1 h without pH change at 125-129 or 134-147 days of gestation within 7 days of spontaneous labor. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia at either age. In moderate hypoxemia at 125-129 days of gestation, there were significant increases of fetal adrenocorticotropic hormone, arginine vasopressin, and cortisol concentrations, and a decreased incidence of fetal breathing movements and eye movements. At 134-147 days of pregnancy, moderate hypoxemia induced a significant increase in adrenocorticotropic hormone, but the response was less than at 125-129 days of gestation. The arginine vasopressin response was similar to that at 125-129 days and there was no significant change in cortisol. There was a significant decrease in fetal breathing movements but not in eye movements. We conclude that a threshold of fetal arterial PO2 drop exists between 5 and 8 mmHg to elicit endocrine or biophysical responses to hypoxemia in fetal sheep at 125-129 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Atélectasie pulmonaire totale au décours d'une anesthésie péridurale

A case is reported of a 69-year-old man who sustained a total atelectasis of his right lung while undergoing ilio-tibial bypass surgery. This patient had a history of chronic obstructive pulmonary disease. The plain chest film showed a possible right-sided segmental atelectasis as well as pleural thickening on the same side. Lung function tests showed up a small obstructive syndrome, with mild hypoxaemia (Pao 2 60,5 mmHg). The procedure was performed under epidural anaesthesia, carried out with 20 ml of 0.5 % bupivacaine and 0.1 mg fentanyl. The upper level of anaesthesia was T4. The patient was sedated with flunitrazepam. He was given oxygen because arterial blood appeared to be somewhat dark. Despite this, the patient became grey, agitated, and had tachypnoea, together with absent breath sounds on the right side. A chest X-ray confirmed the diagnosis of total atelectasis of the right lung. Fiberoptic bronchoscopy was carried out, and a purulent mucous plug was removed. The patient improved and recovered from this episode totally. Blood gases were measured 1 month later ; there was no difference with the preoperative values, except for correction of the hypoxaemia (Pao 2 76 mmHg). The different factors possibly involved in the pathogenesis of the plug are discussed. It is likely that general anaesthesia would not have avoided this complication.

Haemodynamic, pathological, haematological and behavioural changes during endotoxin infusion in equine neonates

The purpose of this study was to evaluate the effects of experimentally induced sublethal endotoxaemia in equine neonates. Four foals, between two and five days of age, were infused intravenously with 0.5 microgram/kg bodyweight of Salmonella typhimurium endotoxin (LPS) over a 5 h period. A four-day-old and a five-day-old foal, similarly infused with sterile isotonic saline, served as controls. Clinical signs were monitored, blood samples obtained for evaluation of selected haematological and biochemical parameters; and haemodynamic parameters were recorded hourly during the infusion, as well as 6 and 24 h post infusion. Depression, anorexia, increased rectal temperature, leucopenia followed by leucocytosis, hypoglycaemia, increased prothrombin time, partial thromboplastin time (APTT), pulmonary artery pressure, pulmonary artery wedge pressure, right atrial pressure, pulmonary and systemic vascular resistance and mild hypoxaemia were consistent findings in the foals receiving endotoxin. There was marked variation over time in the above parameters, during the infusion. Shock was not induced, and the foals appeared to be healthy shortly after the infusion was discontinued. The return to baseline values of body temperature (3 of 4 foals), APTT (1 of 4 foals) and neutrophil count (2 of 4 foals), during endotoxin infusion, suggests induction of early tolerance. The control foals remained alert and the temperature, prothrombin time and fibrinogen remained stable during the study. Hyperglycaemia, transient increased APTT and variations in selected haemodynamic parameters were recorded in the control foals during the infusion.

Severe Hypoxemia and Liver Disease

Severe hypoxemia and orthodeoxia in patients with chronic liver disease is uncommon, but, when present, it is incapacitating. The purpose of this study was to determine the distribution of alveolar ventilation-perfusion (VA/Q) in six patients with mild liver disease and severe hypoxemia (PaO2 at rest in sitting or standing position ranged from 35 to 67 mm Hg). Orthodeoxia was documented with improvement in PaO2 in the supine position in each patient (PaO2 at rest in supine position ranged from 46 to 75 mm Hg). VA/Q distribution was measured by the multiple inert gas elimination technique. The dispersion of VA/Q was increased with small portions of the cardiac output (0.5 to 14.8%) perfusing low VA/Q areas (O less than VA/Q less than 0.1). Another major finding was a large right-to-left shunt (VA/Q less than 0.005) that ranged from 4 to 28%. The VA/Q mismatching and the right-to-left shunt both contributed to the hypoxemia. The predicted PaO2 was 5.5 mm Hg (p less than 0.01) larger than the measured PaO2. In each patient, the mean pulmonary artery pressure was low and the cardiac output was elevated. These results show that the low PaO2 in these patients was due to both increased right-to-left shunt and VA/Q mismatching, but impaired diffusion could not be ruled out.

Isogenic group B streptococci devoid of capsular polysaccharide or beta-hemolysin: pulmonary hemodynamic and gas exchange effects during bacteremia in piglets.

Group B beta-hemolytic streptococcus (GBS) causes thromboxane (Tx)-associated pulmonary hypertension and hypoxemia in neonatal animals and human infants. The components of GBS that induce these features of sepsis are incompletely characterized. The capsular polysaccharide has been implicated based on the effects of GBS extracts. We used isogenic mutants of a parent GBS strain (COH 31 r/s) devoid of capsular polysaccharide or beta-hemolysin to determine if these components caused the acute features of GBS bacteremia. In neonatal piglets, we observed a similar increase in pulmonary vascular resistance (PVR, mm Hg/L/min) during a 1 h infusion at 5 x 10(8) colony-forming unit/kg/h of COH 31 r/s (n = 5, 11.6 +/- 1.4 to 67.1 +/- 17.9), an isogenic GBS mutant devoid of type III CP (n = 5, 12.5 +/- 1.4 to 56.9 +/- 5.0), and an isogenic GBS mutant devoid of beta-hemolysin (n = 4, 11.0 +/- 1.9 to 51.9 +/- 7.9). All three GBS strains caused increases in blood TxB2 levels, mild arterial hypoxemia, mild reduction in mixed venous PO2, and a 30-40% reduction in cardiac output after a 1 h infusion. The Tx-synthase inhibitor, dazmegrel, completely reversed pulmonary hypertension, and partially reversed arterial hypoxemia and TxB2 levels to baseline values for all GBS strains. In six additional piglets, infusion of polystyrene beads of similar size to GBS at a dose of 5 x 10(8) beads/kg/h caused no changes in gas exchange or blood TxB2 levels, but a mild increase in PVR (13.3 +/- 2.0 to 17.7 +/- 3.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological effects of etorphine, acepromazine and xylazine in the scimitar horned oryx (Oryx dammah)

Scimitar horned oryx (Oryx dammah), kept under confined and unconfined conditions were immobilised with etorphine in combination with acepromazine or xylazine or both, and with xylazine alone. Both groups of animals were successfully sedated with etorphine and xylzine, with or without acepromazine, although hypothermia and mild hypoxaemia and a fall in packed cell volume were frequently noted. Xylazine alone produced a dose dependent degree of sedation in semitame subadult animals kept in confinement, but only slight depression in their wild, unconfined counterparts. If xylazine was not included in the immobilising mixture induction was traumatic and full sedation not achieved. Heart rates and arterial pressures (systemic and pulmonary) were also monitored but no remarkable changes were noted. The only abnormalities in blood biochemistry were raised aspartate transminase and creatine kinase. Ruminal regurgitation could be a major problem if endotracheal intubation was not achieved early in the procedure.

Pulmonary hemodynamics, gas exchange, and the severity of emphysema as assessed by quantitative CT scan in chronic bronchitis and emphysema.

We have used the CT transthoracic scan to measure regional lung density in vivo, as our previous studies have shown that this correlates with the increase in size of distal air spaces, which is a defining characteristic of emphysema. We have studied 32 patients with chronic airflow limitation (FEV1, 15 to 68% predicted) caused by chronic bronchitis and emphysema (synonym, COPD), with a wide range of arterial PO2 (38 to 90 mm Hg) and PCO2 (32 to 63 mm Hg) while breathing air at rest. We could find no significant relationships between the extent of emphysema (as assessed in vivo by the EMI number defining the lowest fifth percentile of the CT density histogram of the lung fields) and either arterial blood gas tensions, mean pulmonary arterial pressure, cardiac output, or calculated total pulmonary vascular resistance while at rest (n = 32) or during supine leg exercise (n = 29). We conclude that the extent of emphysema does not correlate with the clinical or pathologic features of the "pink and puffing" (i.e., mild hypoxemia, no CO2 retention, no pulmonary hypertension, etc.) or "blue and bloated" (i.e., hypoxemia, CO2 retention, pulmonary hypertension) pattern of patients with COPD nor to the spectrum of hemodynamic and gas exchange abnormalities that commonly occur in patients between these two extreme examples. Thus, "pink puffers" should not be equated with "the emphysematous" pattern of this disease. Although these clinicophysiologic patterns remain valid as descriptions, they do not relate to the extent of underlying emphysema in COPD.

Pulmonary Vascular Hemodynamics in Chronic Lung Disease Patients with and without Oxyhemoglobin Desaturation During Sleep

Nonapneic, nocturnal oxyhemoglobin desaturation (NOD) during rapid-eye-movement (REM) sleep has been proposed as a predecessor and possible etiologic factor in the development of pulmonary hypertension in patients both with restrictive and obstructive chronic lung disease. The association between abnormal waking cardiopulmonary hemodynamics and NOD has not been established in patients with mild daytime hypoxemia. Gas exchange, pulmonary function, red cell mass, radionuclide gated cardiac ejection fraction, and supine cardiopulmonary hemodynamics were examined in 36 patients with chronic lung disease. All had a daytime PaO2 greater than 60 mm Hg and REM sleep-related NOD for greater than 5 minutes, to 85 percent or lower. These data were compared to those from 13 subjects with similar symptoms and objective measures of pulmonary dysfunction but without evidence of NOD. Patients with NOD showed more end organ evidence of hypoxemia and more abnormal cardiopulmonary hemodynamics than patients with similar degrees of lung disease but without NOD. The relative role of daytime vs nocturnal hypoxemia in inducing hemodynamic differences between groups cannot be determined from this study.

Effect of hypoxia on diaphragm blood flow, oxygen uptake, and contractility.

Recent studies examining the effects of hypoxia on diaphragm function have reached conflicting conclusions, with some reports suggesting an adverse effect of even mild hypoxemia while others indicate that the diaphragm may be extremely resistant to hypoxic stress. Diaphragm tension was not, however, directly measured nor was diaphragm length controlled in these previous reports, and it seems possible that methodologic limitations may have been responsible for these discrepant results. The purpose of the present study was to examine the effects of graded, steady-state hypoxia on diaphragm blood flow, oxygen extraction, oxygen consumption, and contractility using an in situ canine diaphragm strip preparation that permitted direct and continuous measurement of diaphragm length, tension, and blood flow. Measurements were made with the diaphragm at rest, during normoxia (PaO2, 90 to 160 mm Hg), mild hypoxia (PaO2, 45 to 60 mm Hg), and severe hypoxia (PaO2, 25 to 35 mm Hg); measurements were made with the diaphragm at rest, during rhythmic contractions at a tension time index (TTI) of 0.05, and with contractions at a TTI of 0.15. Decreases in arterial oxygenation resulted in progressive increases in blood flow and in the fractional extraction of oxygen in both resting and contracting diaphragm strips. At all levels of activity tested, blood flow and fractional extraction increased sufficiently to keep diaphragm oxygen consumption constant despite reductions in arterial oxygen content. Diaphragm contractility, as assessed from the tension generated in response to a range of electrical stimuli (1 to 80 Hz), was unaffected by hypoxia for trials performed with the diaphragm at rest and contracting at a TTI of 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Intralipid effect on normal and hypoxic remodeled rat pulmonary vasculature.

Intralipid (IL) infusion has been associated with pulmonary vasoconstriction and decreased oxygenation and may worsen preexisting pulmonary vascular changes. To investigate this, we infused IL or 0.9% saline for 1 wk in normal Sprague-Dawley rats and in rats with vascular changes induced by a previous 2-wk exposure to chronic hypobaric hypoxia (air at 380 mmHg). At postmortem we quantitatively evaluated arterial changes in the left lung by light microscopy and alterations in endothelial cells in the right lung by electron microscopy. In rats maintained in room air, 1-wk IL infusion resulted in extension of muscle into alveolar wall and duct arteries (P less than 0.001 for both), medial hypertrophy of arteries 50-99 microns external diameter (P less than 0.01), reduced arterial density (P less than 0.05), and an increase in volume density of endothelial smooth endoplasmic reticulum (P less than 0.05). In post-hypoxia rats, however, IL infusion did not induce further progression of the more severe arterial and endothelial changes observed. To determine whether IL-associated vascular abnormalities may be related to vasoconstriction, different rats were instrumented under pentobarbital sodium anesthesia with indwelling cardiovascular catheters and, 2 days later, with the animals fully conscious, the hemodynamic response assessed. An acute 15-min IL infusion caused a significant increase in pulmonary artery pressure and mild hypoxemia (P less than 0.05 for both) in room air rats but not in the posthypoxia group. This response was not, however, sustained over a 2-day IL infusion. Thus IL induces pulmonary vascular abnormalities that do not appear to be related to vasoconstriction or hypoxemia. We speculate that differences in endothelial metabolism of IL in room air and posthypoxia rats may explain the lack of IL-related abnormalities in the latter group.

Right ventricular performance and pulmonary haemodynamics in adolescent and adult patients with cystic fibrosis.

A combined haemodynamic and radionuclide approach was used to evaluate right ventricular performance in 16 adolescent and adult patients with cystic fibrosis (CF). There were nine patients with mild arterial hypoxaemia (PaO2 greater than 80% of predicted) and normal resting pulmonary artery pressure and seven patients with severe arterial hypoxaemia (PaO2 less than 70% of predicted) and resting pulmonary arterial hypertension (PH). The right ventricular ejection fraction (RVEF) by equilibrium angiocardiography using krypton 81m as a tracer and stroke volume index (SVI) by thermodilution techniques were measured simultaneously and right ventricular end-diastolic and end-systolic volumes were derived. RVEF was normal in CF patients without PH (58.9 +/- 7.2%) but was reduced in those with PH (45.4 +/- 2.6%). There was a statistically significant inverse linear correlation between RVEF and afterload as assessed by mean pulmonary artery pressure (Pap: r = -0.76) and pulmonary vascular resistance (PVR: r = -0.78), indicating that RVEF ist afterload-dependent. Right ventricular function, however, as assessed by right ventricular end-systolic pressure-volume relations was even higher in CF patients with PH, indicating preserved or even increased right ventricular function in the face of an increased afterload stress.

Chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is equated with chronic bronchitis and emphysema as one disease entity. In COPD airflow limitation is relatively persistent--unlike asthma. Tests for "small-airways disease" form no part of routine practice, for their accuracy in detecting pathological change is debatable. The proteolytic theory of the pathogenesis of emphysema highlights the role of neutrophil elastase, antielastases, oxidants, antioxidants, and thus of potential new treatments. Clinical features of COPD include breathlessness, cough, and sputum, with airflow obstruction and lung hyperinflation. The differential diagnosis includes bronchiectasis, cystic fibrosis, and pulmonary hypertension, but pulmonary fibrosis, etc., is distinguished by radiological infiltrates. Plain chest radiography cannot reliably diagnose emphysema in life, but a new method measuring lung density from the computed tomographic (CT) scan allows location, quantitation, and diagnosis of emphysema (defined by enlargement of distal air spaces) in humans in life. "Pink puffers" with breathlessness, hyperinflation, mild hypoxemia, and a low PCO2 are contrasted with "blue bloaters" with hypoxemia, secondary polycythemia, CO2 retention, and pulmonary hypertension and cor pulmonale. Antismoking measures are a major aim in management. A bronchodilator regimen combining a slow-release oral theophylline with an inhaled beta 2-agonist, ipratropium, and high-dose inhaled steroids is proposed because even modest improvement in obstruction can help these patients. In acute exacerbations with purulent sputum, antimicrobials against Streptococcus pneumoniae and Hemophilus influenzae are used with controlled oxygen therapy aiming to keep the arterial PO2 over 50 mm Hg without the pH falling below 7.25. Influenza prophylaxis is recommended, but pneumococcal vaccination remains debatable. Chronic under-nutrition in "emphysema" implies controlled trials of feeding regimens--but these remain to be assessed. Long-term oxygen therapy is the only treatment known to prolong life in blue bloaters, and oxygen concentrators and transtracheal oxygen delivery are discussed. Pulmonary vasodilators (e.g., beta 2-agonists, hydralazine, nifedipine, angiotensin-converting enzyme [ACE] inhibitors, etc.) have not yet been proved to provide long-term reduction in pulmonary arterial pressure. Blue bloaters have severe nocturnal hypoxemia in rapid eye movement (REM) sleep that is corrected by oxygen or the investigational drug almitrine.(ABSTRACT TRUNCATED AT 400 WORDS)