Comparison of three oxygen delivery systems during exercise in hypoxemic patients with chronic obstructive pulmonary disease.

Oxygen therapy improves submaximal exercise tolerance in hypoxemic patients with chronic obstructive pulmonary disease (COPD). This study compared the standard nasal cannula, reservoir nasal cannula, and a demand flow device in 15 male hypoxemic patients with COPD. On six separate occasions each subject used, in a randomized order, all three systems while completing incremental cycle ergometry and a test circuit composed of tasks that simulate activities of daily living. Oxygen flow required during exercise was 1.8 +/- 0.9 and 2.8 +/- 0.7 L/min for reservoir nasal cannula and standard nasal cannula use, respectively (p < 0.0001). The effect of the three oxygen delivery systems on oxygen saturation (Spo2) during the last 30 s of exercise varied with type of activity. Only during demand flow device use while undressing and dressing was the subjects' Spo2 (90 +/- 3%) significantly lower (p = 0.019). There was a trend toward lower Spo2 with the demand flow device (p = 0.103) during arm work above shoulder level. Although not statistically significant, reservoir nasal cannula use resulted in consistently lower tidal volume and minute ventilation during test circuit activities. Exercise tolerance was not significantly different between the three oxygen delivery systems.

Effects of oral albuterol on serum lipids and carbohydrate metabolism in healthy men.

beta(2)-Selective adrenergic agonists are used in the management of bronchial asthma and preterm labor. Due to their ability to increase muscle strength and size in animal models, new applications for these agents are also being explored for neuromuscular disorders and in rehabilitation. However, the effects of long-term beta(2)-agonist administration on lipoprotein and carbohydrate metabolism are incompletely understood. This investigation evaluated the effects of a beta(2)-agonist, albuterol, on serum lipids and carbohydrate homeostasis in eight healthy nonsmoking men aged 24 to 61 years. Collection of fasting blood samples was completed in duplicate on separate days at baseline, during 14 days of oral albuterol administration (Proventil Repetabs, 8 mg twice daily; Schering Pharmaceuticals, Kenilworth, NJ) and during a 7-day washout period. Carbohydrate homeostasis was evaluated using the minimal model technique at the end of the baseline and albuterol periods. Fasting glucose and insulin, intravenous glucose tolerance, acute insulin response to intravenous glucose (AIRg), insulin sensitivity (Si), and glucose effectiveness (Sg) were not significantly changed during albuterol administration. Significant alterations (P < or = .02) were observed in total cholesterol ([TC] -9.1% +/- 2.5%), low-density lipoprotein cholesterol ([LDL-C] -15.0% +/- 2.9%), and high-density lipoprotein cholesterol ([HDL-C] +10.4% +/- 3.2%) concentrations, as well as the TC/HDL-C (-17.4% +/- 2.6%) and LDL-C/HDL-C (-22.9% +/- 2.4%) ratios. During washout, TC and LDL-C returned to baseline levels, whereas HDL-C remained elevated by 5.8% +/- 2.4% (P < .05). Thus, albuterol administration was associated with favorable changes in the serum lipid profile without marked impairment of glucose tolerance or its physiologic determinants.

Magnesium sulfate in exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease are commonly seen and difficult to treat. We sought to determine the bronchodilator efficacy of magnesium sulfate in this situation, as this compound is helpful in acute asthma. METHODS: Subjects who came to either of two Veterans Affairs emergency departments were randomized in a double-blind fashion to receive either 1.2 g of magnesium sulfate or placebo over 20 minutes after they first received albuterol, 2.5 mg by nebulization. Peak expiratory flow, dyspnea scores, arterial hemoglobin oxygen saturation by pulse oximetry, maximal inspiratory and expiratory pressures, and vital signs were monitored for 45 minutes after the start of magnesium sulfate or placebo treatment. RESULTS: Seventy-two individuals were studied. The peak expiratory flow increased 16.6% +/- 27.7% (mean +/- SD) in both groups after the initial albuterol treatment, from 121.2 +/- 55.7 L/min to 136.9 +/- 63.9 L/min. The peak expiratory flow increased from 136.7 +/- 69.7 L/min at the start of the infusion to 162.3 +/- 76.6 L/min at 30 minutes and 161.3 +/- 78.7 L/min at 45 minutes with magnesium sulfate treatment. The peak expiratory flow was 137.0 +/- 58.6 L/min on initiation of the intravenous infusion, 143.0 +/- 72.7 L/min at 30 minutes, and 143.3 +/- 70.5 L/min at 45 minutes in the placebo group. The difference in peak expiratory flow from initiation of the infusion to 30 and 45 minutes later (calculated as means of the 30- and 45-minute values) was significantly different for the two groups (25.1 +/- 35.7 L/min vs 7.4 +/- 33.3 L/min; P = 0.3); the difference was also significant when expressed as percentage increase (22.4% +/- 28.5% vs 6.1% +/- 24.4%; P = .01). There was a statistically nonsignificantly trend toward a reduced need for hospitalization in the magnesium sulfate group as compared with the placebo group (28.1% vs 41.9%; P = .25). There were no significant changes in the other parameters with either treatment. CONCLUSION: Magnesium sulfate, 1.2 g over 20 minutes after beta-agonist administration, is safe and modestly efficacious in the treatment of acute exacerbations of chronic obstructive pulmonary disease, and its bronchodilator effect is greater than that of a beta-agonist given alone and lasts beyond the period of magnesium sulfate administration.

Mirror-image tumors in mirror-image twins.

Genetic factors are known to play a role in causing lung cancer. Twin cases of bronchioloalveolar, squamous, and anaplastic bronchogenic carcinoma have been previously reported. We describe mirror-image twins with adenocarcinoma of the lung occurring in mirror-image locations. They shared smoking and an occupational risk, carpentry, in addition to identical genetic backgrounds.

Magnesium sulfate potentiates several cardiovascular and metabolic actions of terbutaline.

beta-Adrenergic agonists are useful for the emergency treatment of asthma. Recently, magnesium sulfate (MgSO4) has also been shown to be efficacious in this situation. beta-Agonists have unwanted cardiovascular and metabolic actions: increased systolic blood pressure, corrected QT interval (QTc), serum glucose and insulin, and decreased RR interval, diastolic blood pressure, serum potassium, phosphate, and calcium. As beta-agonists and MgSO4 quite possibly will be used in combination, we sought to determine how MgSO4 would affect these actions. Healthy young male adults were administered two doses of terbutaline sulfate, 0.25 mg subcutaneously, 30 min apart on two separate occasions, in a randomized, double-blind fashion. On one occasion, 4 g of MgSO4 was administered intravenously over the same 30-min period. On the other, normal saline solution was given as a placebo. Cardiovascular and metabolic variables were measured sequentially for 2 h. Data at 60 min with p values given for a summation of all time points are as follows: MgSO4 increased terbutaline's effects on the RR interval by 0.09 s, p < 0.0001; QTc interval by 0.01 s, p < 0.0007; diastolic blood pressure by 8 mm Hg, p = 0.0001; serum calcium by 0.13 mg/dl, p = 0.01; and glucose by 9 mg/dl, p < 0.0001. MgSO4 also mitigated the systolic blood pressure elevating the effect of terbutaline by 5 mm Hg (p = 0.007). The magnitude of the response potentiations was modest. We conclude that combining terbutaline and MgSO4 is unlikely to result in serious short-term adverse events, if used acutely in patients with relatively normal cardiac and metabolic function. MgSO4 may act by potentiating the effect of beta-agonists on magnesium requiring enzymes such as adenyl cyclase.

Performance of a reservoir nasal cannula (Oxymizer) during sleep in hypoxemic patients with COPD.

STUDY OBJECTIVE: To determine whether a reservoir nasal cannula (RNC) (Oxymizer) provides an arterial hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) equivalent to that provided by the standard nasal cannula (SNC) during sleep in hypoxemic patients with COPD while reducing oxygen flow requirement and cost. DESIGN: The study took place in a sleep laboratory for three nights, with the first night for acclimatization to the new sleeping environment. In a repeated-measures design, on the second and third nights, subjects used the SNC for one night and the RNC on another night. The order in which they received the two devices was counterbalanced. SUBJECTS: The subjects were patients with COPD who had a stable PaO2 of 55 mm Hg or less or had a value of 56 to 59 mm Hg with evidence of cor pulmonale or polycythemia (or both) and an FEV1/FVC of less than 70 percent. INTERVENTIONS: A pulse oximeter was used to measure SpO2. An arterial blood gas measurement was taken on each night while the patients with COPD were receiving oxygen therapy via the assigned device. An EEG machine was used to record measurements of electro-oculography, chin electromyography (EMG), anterior tibialis EMG and EEG. MEASUREMENTS AND MAIN RESULTS: There was a statistically significant difference between mean SpO2 during sleep (RNC, 91 percent; SNC, 93 percent; F = 7.89; p = 0.01). Nocturnal SpO2 was less than 90 percent for 24.2 percent of the time with the RNC and for 17.5 percent of the time with the SNC (F = 5.41; p = 0.03), but there was no significant difference in the amount of time that SpO2 was less than 85 percent. Compared to the SNC, in 4 of 26 patients with COPD, the RNC performed better; in 12 patients with COPD, the RNC performed the same, and in 10 patients with COPD the RNC performed worse during sleep. Sleep parameters were not significantly different between the two devices. CONCLUSIONS: The difference of 2 percent in mean SpO2 is within the range of SpO2 measurement error. Therefore, the two devices are equally effective when the sample is considered as a whole. Nighttime oximetry is necessary prior to prescription, since nighttime efficacy of the RNC cannot be predicted on the basis of daytime pulse oximetry.

Pharmacotherapy for asthma and chronic obstructive pulmonary disease. Current thinking, practices, and controversies.

A number of new medications for treatment of asthma and chronic obstructive pulmonary disease have been developed in recent years. However, serious issues persist in the management of these illnesses. Prevalence, morbidity, and mortality of asthma are increasing despite the introduction of these new agents. Airflow obstruction is only partially reversible in chronic obstructive pulmonary disease, and drug treatment can only mitigate disability incompletely. Drug toxicity is also an important concern. The five classes of agents (beta-adrenergic agonists, anticholinergic agents, theophylline, cromolyn, and corticosteroids) available for treatment are examined in this review, emphasizing efficacy and toxicity. Less commonly used agents and newly developed compounds that are still investigational are also discussed.

Cholinergic bronchomotor tone in COPD. Estimates of its amount in comparison with that in normal subjects.

The use of anticholinergic bronchodilators in COPD is based on the reversal of cholinergic bronchomotor tone. There is little information about the magnitude of cholinergic tone in patients with COPD as compared with normal subjects. As an index of the amount of cholinergic tone we measured the maximum increase in FEV1 following administration of an optimal dose of the anticholinergic agent atropine methonitrate. The study included nine normal nonsmoking subjects, ten normal smokers and 22 subjects with mild to moderately severe COPD. We found that normal nonsmokers had smallest increases in FEV1 following atropine methonitrate administration. Responses of subjects with airway disease were progressively greater. Greatest responses occurred in the group of subjects with prebronchodilator FEV1 values less than 55 percent of predicted. The most plausible explanation for this is that cholinergic tone in COPD is increased in proportion to the severity of airway disease. Other explanations are possible.

Dose response to ipratropium as a nebulized solution in patients with chronic obstructive pulmonary disease. A three-center study.

We performed a dose-response study of ipratropium bromide as a nebulized solution in patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind crossover format. Five doses from 0.05 to 0.6 mg of ipratropium bromide as a nebulized solution, the standard dose of ipratropium bromide by metered-dose inhaler, 40 micrograms, and placebo were given in random order on separate days. End points were the maximal increase in FEV1 and FVC, and the area under the FEV1 and FVC curves in the 8 h after administration of each of the seven treatments. Forty-two patients completed all seven study days. By each of the above end points for FEV1, 0.4 and 0.6 mg of nebulized ipratropium bromide achieved significantly more bronchodilatation than did each of the other treatments. These two doses were not significantly different from each other, suggesting that the optimal dose in this patient population is 0.4 mg. After this dosage, the FEV1 increased by 440 +/- 194 (mean +/- 1 SD) ml at peak effect between 1 and 2 h, and significant bronchodilatation persisted for 6.5 h. Ipratropium bromide by metered-dose inhaler (40 micrograms) was equivalent to approximately 0.1 mg by nebulized solution and achieved only 63 to 73% of the bronchodilatation achieved by optimal doses of the nebulized solution. In terms of FVC, all treatments with ipratropium were significantly better than with placebo. The area under the FVC curve was significantly greater after 0.4 and 0.6 mg of nebulized solution than after other treatments. No significant adverse experiences occurred with any of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic management of obstructive lung disease. Current perspectives.

Pharmacotherapy of obstructive lung disease has improved both quantitatively and qualitatively in recent decades: quantitatively with improvements in adrenergic and methylxanthine drugs and qualitatively with the addition of new classes of drugs, such as steroids, cromolyn, and, most recently, anticholinergic agents. Management of airways disease is based upon several principles: near-normal airways function should be aimed for; long-term, systemic, moderate-to-high-dose corticosteroids should be avoided if at all possible; the judicious use of polypharmacy should be undertaken whenever necessary to provide effective treatment while minimizing drug side effects; and the therapeutic program for a given individual should be tailored to that patient's specific responses to various treatments. Available pharmacologic agents have varying efficacies and adverse effects. The various agents may be used in a number of combinations.

Oxitropium bromide, a new anticholinergic bronchodilator.

Oxitropium bromide (OB) is a quaternary ammonium congener of hyoscine with anticholinergic properties. We studied its bronchodilating properties in 14 patients with chronic obstructive lung disease without features of asthma in whom theophylline and other bronchodilators were withheld. Five doses of OB(20, 40, 100, 200, and 400 micrograms) as well as 150 micrograms of isoproterenol (ISO) and placebo were administered by metered-dose inhaler on separate occasions in a double-blind fashion. Pulmonary function (flow volume loops and airways resistance), blood pressure, and pulse rate were measured at baseline and periodically for eight hours after drug administration. Onset of bronchodilator effect was within five minutes for OB (P less than .025). Duration of action of OB was at least eight hours (P less than .025). The dose response characteristics of OB were examined by correlating the log dose with the areas under the time-FEV1 curve (r = .97, P less than .01), the time-forced vital capacity curve (r = .98, P less than .01), and the time-SGAW curve (r = .83, P less than 0.1). For FEV1, doses of 40 to 400 micrograms were significantly better than placebo and 100 to 400 micrograms were better than ISO (P less than .01). For forced vital capacity, all doses of OB were better than placebo (P less than .05). For SGAW, the response to the 100- and 400-micrograms doses were significantly better than placebo and isoproterenol (P less than .05). There were no significant effects of OB on pulse, blood pressure, or electrocardiogram. No side effects were noted from the use of OB.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the parasympathetic system in airway obstruction due to emphysema.

To study the relative contributions of parasympathetic and sympathetic mechanisms in airway obstruction in patients with emphysema, we gave supramaximal doses of anticholinergic and adrenergic agents in sequence and in combination. Serial doses of one agent were administered to achieve a plateau of bronchodilatation; after that the other agent was administered. The plateau achieved with the anticholinergic agent (atropine methonitrate) was significantly higher than that achieved with the adrenergic agent (salbutamol). When the adrenergic agent was given first, additional bronchodilatation was achieved with subsequent use of the anticholinergic agent. When the anticholinergic agent was given first, no additional bronchodilatation was achieved with subsequent administration of the adrenergic agent. When both agents were given simultaneously, the degree of bronchodilatation was virtually identical to that obtained with the anticholinergic agent alone. Tests sensitive to small-airway and large-airway function and lung volumes gave essentially the same results. Thus, all achievable bronchodilatation was obtained with the anticholinergic agent alone. These results suggest that the two classes of agents produce bronchodilatation through a common cholinergic pathway in emphysema, and support the concept that parasympathetic activity is the dominant reversible component of airway obstruction in this disease.

Anticholinergic, antimuscarinic bronchodilators.

The anticholinergic, antimuscarinic compounds are potent and hitherto neglected bronchodilators. Although atropine itself has drawbacks, principally related to its rapid absorption and consequent systemic side effects, its quaternary ammonium congeners, atropine methonitrate and ipratropium bromide, are poorly absorbed. When given by inhalation, they are as effective bronchodilators as atropine is, but longer acting and much less prone to side effects. They act predominantly at a site that is different from adrenergic agents and thus afford an alternative, complementary approach to the treatment of airways obstruction. In stable asthmatic subjects, ipratropium is almost as potent a bronchodilator as beta 2-adrenergic agents are. In patients with chronic bronchitis and emphysema, it is more potent than beta 2-adrenergic agents are. In both conditions, its combination with other bronchodilators adds significantly to the level and duration of bronchodilatation. It may also be occasionally useful in counteracting bronchospasm caused by specific stimuli, such as cold air and exercise, and particularly that caused by inadvertent beta-adrenergic blockade. By inhalation, ipratropium is relatively free of side effects, even in doses as much as 20 times those that produce maximal bronchodilatation. It does not significantly affect mucus production, viscosity, or clearance, problems for which atropine is suspect. Nor does it produce tremor and tachycardia, as do adrenergic agents. It can also probably be safely used in patients with glaucoma and bladder neck obstruction, unlike atropine. Ipratropium will probably find its major application in the long-term management of chronic bronchitis and emphysema, and in asthmatic patients who are poorly controlled by, or who experience troublesome side effects from, adrenergic agents.