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Biomedical subjects

G T Ferguson

Publications and source records attributed to G T Ferguson.

At least 19 recordsLinked to original sources
PubMed2000

Update on pharmacologic therapy for chronic obstructive pulmonary disease.

As described throughout this article, significant improvements continue to occur in the pharmacologic management of COPD. These improvements range from improved medication targeting to better understanding of mechanisms of action, to better delivery of medications, to lower side effects. New areas of pharmacologic intervention, if not ready for use today, hold great promise for the not-too-distant future. In addition to the many agents described here, multiple mediator antagonists and anti-inflammatory agents are also under investigation for use in COPD. Interestingly, repair of alveolar tissue may be possible. Indeed, preliminary animal studies suggest that retinoic acid may be able to induce regeneration of lung alveoli. Overall, more effort is needed to broaden awareness and provide for the appropriate diagnosis of COPD, better explain pharmacologic therapies for COPD, simplify and disseminate guidelines, and highlight key differences between asthma and COPD, including their treatment strategies. As interest in COPD continues to grow, future updates on COPD management will continue to add new pharmacologic options for this devastating and preventable disease.

Adrenal Cortex Hormones↗
PubMed2000

Recommendations for the management of COPD.

Three sets of guidelines for the management of COPD that are widely recognized (from the European Respiratory Society [ERS], American Thoracic Society [ATS], and British Thoracic Society [BTS]) are reviewed and compared. None of the documents uses classic evidence-based documentation, and, in many instances, the recommendations are empiric because of a lack of scientific evidence. Overall, there is strong agreement between the documents. All three guidelines recommend inhaled bronchodilators as first-line therapy. Anticholinergics are noted to be well tolerated, although potential problems with beta(2)-agonists are mentioned. The ERS and BTS suggest that inhaled corticosteroids may be of value in patients documented to be steroid responders, whereas the ATS does not recommend their use at all. All three guidelines support the use of oxygen and pulmonary rehabilitation. There are varying levels of disagreement between the guidelines related to the role of spirometry, stratification of disease severity, and the use of theophylline and systemic corticosteroids. Other differences include the role for nebulizers and metered-dose inhalers, secretion clearance methodologies, and the treatment of acute COPD exacerbations and acute respiratory failure. All three guidelines agree that more research is needed to improve our understanding and management of COPD.

Adrenal Cortex Hormones↗
PubMed2000

Office spirometry for lung health assessment in adults: A consensus statement from the National Lung Health Education Program.

COPD is easily detected in its preclinical phase using spirometry, and successful smoking cessation (a cost-effective intervention) prevents further disease progression. This consensus statement recommends the widespread use of office spirometry by primary-care providers for patients >/= 45 years old who smoke cigarettes. Discussion of the spirometry results with current smokers should be accompanied by strong advice to quit smoking and referral to local smoking cessation resources. Spirometry also is recommended for patients with respiratory symptoms such as chronic cough, episodic wheezing, and exertional dyspnea in order to detect airways obstruction due to asthma or COPD. Although diagnostic-quality spirometry may be used to detect COPD, we recommend the development, validation, and implementation of a new type of spirometry-office spirometry-for this purpose in the primary-care setting. In order to encourage the widespread use of office spirometers, their specifications differ somewhat from those for diagnostic spirometers, allowing lower instrument cost, smaller size, less effort to perform the test, improved ease of calibration checks, and an improved quality-assurance program.

Adult↗
PubMed2000

Office spirometry for lung health assessment in adults: a consensus statement from the National Lung Health Education Program.

Chronic obstructive pulmonary disease (COPD) is easily detected in its preclinical phase using spirometry, and successful smoking cessation (a cost-effective intervention) prevents further disease progression. This consensus statement recommends the widespread use of office spirometry by primary-care providers for patients > or = 45 years old who smoke cigarettes. Discussion of the spirometry results with current smokers should be accompanied by strong advice to quit smoking and referral to local smoking cessation resources. Spirometry also is recommended for patients with respiratory symptoms such as chronic cough, episodic wheezing, and exertional dyspnea in order to detect airways obstruction due to asthma or COPD. Although diagnostic-quality spirometry may be used to detect COPD, we recommend the development, validation, and implementation of a new type of spirometry-office spirometry--for this purpose in the primary-care setting. In order to encourage the widespread use of office spirometers, their specifications differ somewhat from those for diagnostic spirometers, allowing lower instrument cost, smaller size, less effort to perform the test, improved ease of calibration checks, and an improved quality-assurance program.

Adult↗
PubMed1999

The combination of ipratropium and albuterol optimizes pulmonary function reversibility testing in patients with COPD.

STUDY OBJECTIVES: To determine whether the combination of ipratropium bromide and albuterol results in greater and more consistent pulmonary function test (PFT) response rates than ipratropium bromide or albuterol alone in patients with COPD. DESIGN: Retrospective review of two recently completed 3-month, randomized, double-blind, parallel, multicenter, phase III trials. SETTING: Outpatient. PATIENTS: A total of 1,067 stable patients with COPD. INTERVENTIONS: Ipratropium bromide (36 microg qid), albuterol base (180 microg qid), or an equivalent combination of ipratropium bromide and albuterol sulfate (42 microg and 240 microg qid, respectively). MEASUREMENTS AND RESULTS: PFT response rates were analyzed using 12% and 15% increases in FEV1 compared with baseline values and were measured in the various treatment groups on days 1, 29, 57, and 85 in these trials. Regardless of whether a 12% or a 15% increase in FEV1 was used to define a positive response, an equivalent combination of ipratropium bromide and albuterol sulfate was superior to the individual agents (p < 0.05; all comparisons within 30 min). In addition, a 15% or more increase in FEV1 was seen in > 80% of patients who received the combination of ipratropium and albuterol sulfate during the initial PFT and continued to be observed 3 months after initial testing. CONCLUSIONS: Use of a combination of ipratropium bromide and albuterol sulfate is superior to the individual agents in identifying PFT reversibility in patients with COPD.

Adrenergic beta-Agonists↗
PubMed1998

Screening and early intervention for COPD.

Chronic obstructive pulmonary disease is on the increase. Therapeutic improvement is limited by the irreversible nature of lung tissue loss. Basic lung function tests can detect early loss of function, which may facilitate smoking cessation and other interventions likely to delay disease progression. The advent of inexpensive portable spirometers promises to permit such testing in the primary care physician's office.

Adult↗
PubMed1998

Improved exercise performance following lung volume reduction surgery for emphysema.

Lung volume reduction surgery (LVRS) for emphysema has been suggested to improve patient lung function and activity. The short-term impact of LVRS on exercise performance was evaluated using maximal and submaximal steady-state exercise testing in 27 patients with severe hypoxemic chronic obstructive pulmonary disease (COPD), along with measurements of patient function, dyspnea, and quality of life. LVRS significantly improved exercise performance, due to ventilatory improvements associated with increased ventilatory reserve, enhanced tidal volume recruitment, and improved alveolar ventilation. Preoperative measurements of ventilatory reserve and dead space ventilation during exercise testing were closely associated with improved exercise performance. Improvements in patient dyspnea, walk distances, and quality of life also occurred following LVRS and were associated with improvements in exercise performance. Surgical mortality from LVRS was low (4%), but short-term all-cause mortality was increased (19%). Short-term mortality was associated with reduced expiratory muscle strength and markedly elevated dead space ventilation. We conclude that LVRS produces significant improvements in exercise performance, dyspnea, and quality of life in selected patients with COPD. Physiologic prediction of patients most likely to survive for an extended period and have significant benefit following LVRS may also be possible.

Adult↗
PubMed1998

Management of COPD. Early identification and active intervention are crucial.

Medical management of COPD begins with an awareness of risk factors and identification of at-risk patients. Once disease is identified, patient and family education, a smoking cessation program, and an appropriate bronchodilator regimen should be initiated. Airway secretions and infections should be minimized, hypoxemia corrected, and other secondary physiologic disturbances evaluated when appropriate. Participation in a comprehensive pulmonary rehabilitation program can markedly improve symptoms, function, exercise performance, and quality of life. The results are a reduction in patient limitations, medical expenses, and dependence on medical facilities and caregivers.

Anti-Inflammatory Agents↗
PubMed1995

Respiratory failure due to altered central drive during inspiratory loading in rabbits.

Mechanisms of respiratory muscle dysfunction leading to respiratory failure during incremental inspiratory threshold loading were studied in unbound spontaneously breathing rabbits during light and deeper anesthesia. Low or high frequency contractile fatigue was not found at the point of respiratory failure in any of the animals. On the other hand, alterations in central drive to the diaphragm played a dominant role in the observed respiratory failure. In animals receiving light anesthesia the intensity of central drive increased with loading, but then fell as respiratory failure approached. In all animals the intensity of central drive at peak activation and at the point of respiratory failure was submaximal, in spite of the diaphragm's ability to generate additional forces. In addition, the time tension index of the diaphragm rose in response to increasing loads to a level reported to produce contractile fatigue, at which time the index peaked and then fell in spite of increasing load demands. The fall in the time tension index as respiratory failure approached was due primarily to a fall in inspiratory time and duty cycle. Ultimately, there was an abrupt cessation in central drive resulting in apnea. These findings suggest that alterations in central drive play a major role in respiratory muscle dysfunction and respiratory failure associated with inspiratory loading in unbound spontaneously breathing rabbits.

Animals↗
PubMed1995

Effects of cortisone and testosterone on diaphragmatic function and biochemistry in the rabbit.

The effects of cortisone and testosterone on in vivo diaphragmatic function and biochemistry were assessed in rabbits to determine whether androgens can prevent the effects of corticosteroids on diaphragmatic function and biochemistry and what mechanisms of muscle function may be altered. Cortisone altered respiratory muscle endurance and diaphragmatic glycogen and lactate levels but had little effect on diaphragmatic strength. Testosterone had no significant impact on diaphragmatic strength, endurance, or biochemistry. However, concomitant administration of testosterone with cortisone blunted the effect of cortisone on respiratory muscle endurance, even though it failed to block the effects of cortisone on diaphragmatic glycogen and lactate levels. Alterations in respiratory muscle endurance were not due to low- or high-frequency contractile fatigue of the diaphragm or diaphragmatic glycogen depletion or lactate accumulation in any of the treatment conditions. On the other hand, alterations in central drive played a dominant role, as evidenced by alterations in inspiratory duty cycle and a falloff in the intensity of central drive during loading. Although the exact mechanisms underlying the alterations in central drive remain unknown, concomitant administration of androgens with corticosteroids blunted the impact of corticosteroids on respiratory muscle function.

Animals↗
PubMed1995

Effects of oxygenation and hypercapnia on diaphragmatic function and central drive during respiratory failure.

The effects of oxygenation and hypercapnia on diaphragmatic function and central drives were assessed during the development of respiratory failure in anesthetized unbound spontaneously breathing rabbits. Oxygenation significantly altered endurance times, whereas hypercapnia had no effect. Isolated high-frequency contractile fatigue of the diaphragm was found in hyperoxic animals; all other animals had no evidence of contractile fatigue. Oxygenation and hypercapnia did not significantly alter the response of breathing frequency or duty cycle to loading. In all animals, there was a falloff in the intensity of central drive before apnea, with intensity of central drive remaining submaximal throughout loading. Oxygenation significantly altered the time and/or load at which drive intensity fell off, although critical blood gas levels were not associated with the falloff in intensity. We conclude that oxygenation influences the development of respiratory failure during inspiratory loading but does not directly explain the alterations is central drive. On the other hand, hypercapnia has no direct effect on respiratory muscle function or central drives during loading to respiratory failure. When the effects of hypoxemia are obviated by hyperoxia, high-frequency contractile fatigue may occur.

Animals↗
PubMed1995

CO2 rebreathing during BiPAP ventilatory assistance.

BiPAP ventilatory assistance can increase minute ventilation and reduce respiratory effort, but does not always reduce PaCO2. We studied the effects of BiPAP ventilatory assistance on PaCO2 and examined specific mechanisms whereby BiPAP ventilatory assistance may not lower PaCO2. BiPAP ventilatory assistance using a non-rebreather valve and volume cycled ventilation at similar settings produced significantly lower PaCO2 than BiPAP ventilatory assistance using a standard exhalation device. The failure of PaCO2 to fall with the standard exhalation device was due to exhalation past the exhalation device into the ventilator tubing, subsequent rebreathing of the exhaled gases, and an increase in dead space ventilation. Use of other fixed-resistance exhalation devices also resulted in exhalation back into the ventilator tubing. Use of a new plateau exhalation device or a non-rebreather valve eliminated CO2 rebreathing and its effect on dead space ventilation. Changing exhalation devices had no significant effect on BiPAP pressure generation or sensing capabilities. Our results indicate that the use of a standard exhalation device during BiPAP ventilatory assistance causes CO2 rebreathing, which can blunt any effect of BiPAP on PaCO2. Use of an appropriate alternative exhalation device can eliminate this problem.

Carbon Dioxide↗
PubMed1994

Use of twitch pressures to assess diaphragmatic function and central drive.

Transdiaphragmatic pressures generated by phrenic nerve twitches have been proposed as a means to assess diaphragmatic function and central drive, but their validity and reliability have not been determined. We evaluated diaphragmatic twitch and twitch occlusion measurements in a rabbit model of diaphragmatic contractile dysfunction and diaphragmatic fatigue to determine whether 1) diaphragmatic twitch pressures accurately assess changes in low- and high-frequency diaphragm trains during the development of, and recovery from, contractile fatigue; 2) twitch occlusion measurements accurately quantify the intensity of central drive to the diaphragm; and 3) twitch measurements are affected by thoracoabdominal binding or twitch potentiation. Single-twitch and 20-Hz double- and triple-twitch pressures accurately reflected changes in low-frequency diaphragm train pressures, whereas only 80-Hz triple-twitch pressures accurately reflected changes in high-frequency trains. Twitch occlusion measurements of central drive closely mirrored central drive as reflected by phrenic nerve recordings and only slightly underestimated the absolute intensity of central drive. Thoracoabdominal binding increased twitch and train pressures, and repetitive electrical stimulations further potentiated twitch pressure. However, twitch potentiation and a lack of thoracoabdominal binding had no effect on twitch measurements of diaphragmatic function during the induction and recovery from fatigue or on twitch occlusion measurements of intensity of central drive. Thus, twitch measurements can be used to accurately assess diaphragmatic low- and high-frequency fatigue and to quantify the intensity of central drive to the diaphragm.

Anesthesia↗
PubMed1993

Nasal continuous positive airway pressure in the treatment of tracheobronchomalacia.

The effect of nasal continuous positive airway pressure (CPAP) was assessed in three patients with tracheobronchomalacia (TBM) who failed conventional medical management. Using physiologic measures of airflow and fiberoptic bronchoscopy, we evaluated expiratory airflow and airway collapse during the acute administration of nasal CPAP. FVC increased and dynamic airway collapse [slow vital capacity minus forced vital capacity (SVC--FVC)] decreased with increasing levels of CPAP. Notching associated with airway collapse was observed in the baseline spirograms of all three patients, and it disappeared with the addition of nasal CPAP. Fiberoptic bronchoscopy confirmed the severity of TBM in each patient and documented an acute improvement in expiratory airway collapse with the addition of nasal CPAP. Intermittent nasal CPAP was then added to the patients' treatment regimens, improving the course of their disease. Specific treatment outcomes varied from patient to patient, but they included improved sputum production, atelectasis, exercise tolerance, and patient symptoms plus reduced need for medical care. These findings suggest that the addition of intermittent nasal CPAP to routine medical therapy may be of benefit to patients with severe TBM unresponsive to conventional medical management.

Adult↗
PubMed1990

Effect of corticosteroids on diaphragm function and biochemistry in the rabbit.

The effects of corticosteroid administration for 2 weeks on diaphragm histology, biochemistry, and function were assessed in the rabbit at rest and during inspiratory loading to respiratory failure, and compared to the extensor digitorum longus and untreated control animals. There were marked pathologic changes in the diaphragm after corticosteroid administration and significant alterations in diaphragm glycogen level (118.7 +/- 2.8 versus 56.2 +/- 1.0 mmol/kg wet weight, p less than 0.01) and lactate level (5.3 +/- 0.3 versus 3.5 +/- 0.4 mmol/kg wet weight, p less than 0.01) with only minimal changes in the skeletal muscle. Although respiratory muscle endurance in the control group increased from 142 +/- 17 min at baseline to 155 +/- 20 at Week 1 and 183 +/- 13 at Week 2 (p less than 0.05), it fell progressively from 135 +/- 19 min at baseline to 99 +/- 5 at Week 1 and 88 +/- 9 at Week 2 (p less than 0.01) in the corticosteroid-treated animals. On the other hand, there was no significant change in resting Pdimax after corticosteroid administration. In addition, there was no significant change in Pdimax, Pdi/Edi ratio, or glycogen level at the point of respiratory failure, but diaphragm lactate levels were increased (8.5 +/- 0.8 versus 5.3 +/- 0.3, p less than 0.05). When variable degrees of diaphragm dysfunction were induced by phrenic nerve pacing and/or thoracoabdominal binding, the degree of biochemical change associated with diaphragm dysfunction was significantly greater in corticosteroid-treated animals. We conclude that corticosteroid administration in the rabbit alters diaphragm histopathology and biochemistry as well as respiratory muscle endurance, but not strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗