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Biomedical subjects

J P Kiley

Publications and source records attributed to J P Kiley.

At least 19 recordsLinked to original sources
PubMed2000

Effects of varying approaches for identifying respiratory disturbances on sleep apnea assessment.

Varying approaches to measuring the respiratory disturbance index (RDI) may lead to discrepant estimates of the severity of sleep-disordered breathing (SDB). In this study, we assessed the impact of varying the use of corroborative data (presence and degree of desaturation and/or arousal) to identify hypopneas and apneas. The relationships among 10 RDIs defined by various definitions of apneas and hypopneas were assessed in 5,046 participants in the Sleep Heart Health Study (SHHS) who underwent overnight unattended 12-channel polysomnography (PSG). The magnitude of the median RDI varied 10-fold (i.e., 29.3 when the RDI was based on events identified on the basis of flow or volume amplitude criteria alone to 2.0 for an RDI that required an associated 5% desaturation with events). The correlation between RDIs based on different definitions ranged from 0.99 to 0.68. The highest correlations were among RDIs that required apneas and hypopneas to be associated with some level of desaturation. Lower correlations were observed between RDIs that required desaturation as compared with RDIs defined on the basis of amplitude criteria alone or associated arousal. These data suggest that different approaches for measuring the RDI may contribute to substantial variability in identification and classification of the disorder.

Adult↗
PubMed1998

Methods for obtaining and analyzing unattended polysomnography data for a multicenter study. Sleep Heart Health Research Group.

This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.

Electroencephalography↗
PubMed1997

The Sleep Heart Health Study: design, rationale, and methods.

The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.

Adult↗
PubMed1996

Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Lung Health Study Research Group.

STUDY OBJECTIVE: To assess cardiovascular conditions and other side effects associated with the use of nicotine polacrilex (NP), 2 mg. DESIGN: A multicentered randomized control trial of early intervention for the prevention of COPD. SETTING: Ten university medical centers in the United States and Canada. PARTICIPANTS: Adult smoking volunteers with evidence of early COPD; 3,923 in intervention and 1,964 controls. INTERVENTION: Smoking cessation program, including NP. MEASUREMENTS: Data on hospitalizations were collected annually. Data on reported NP side effects were collected at 4-month intervals for intervention participants. RESULTS: The rates of hospitalization for cardiovascular conditions and cardiovascular deaths during the 5 years of the study were not related to use of NP, to dose of NP, or to concomitant use of NP and cigarettes. About 25% of NP users reported at least one side effect, but most were very minor and transient. Side effects associated with discontinuance of NP in 5% or more of users included headache, indigestion, mouth irritation, mouth ulcers, and nausea. There was no evidence that concomitant use of NP and cigarettes was associated with elevated rates of reported side effects. Participants in the smoking cessation intervention who received intensive levels of instruction and monitoring of NP use (initially at 12 meetings during 3 months) appeared to report significantly lower rates of side effects (dizziness, headache, and throat irritation) than control participants, presumed to have less instruction and monitoring. CONCLUSIONS: NP, as used in the Lung Health Study, appears to be safe and unrelated to any cardiovascular illnesses or other serous side effects.

Adult↗
PubMed1994

Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study.

OBJECTIVE: To determine whether a program incorporating smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in forced expiratory volume in 1 second (FEV1) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease. DESIGN: Randomized clinical trial. Participants randomized with equal probability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention. SETTING: Ten clinical centers in the United States and Canada. PARTICIPANTS: A total of 5887 male and female smokers, aged 35 to 60 years, with spirometric signs of early chronic obstructive pulmonary disease. INTERVENTIONS: Smoking intervention: intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with continuing 5-year maintenance program to minimize relapse. Bronchodilator: ipratropium bromide prescribed three times daily (two puffs per time) from a metered-dose inhaler. MAIN OUTCOME MEASURES: Rate of change and cumulative change in FEV1 over a 5-year period. RESULTS: Participants in the two smoking intervention groups showed significantly smaller declines in FEV1 than did those in the control group. Most of this difference occurred during the first year following entry into the study and was attributable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small noncumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of the study. CONCLUSIONS: An aggressive smoking intervention program significantly reduces the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV1 that appears to be reversed after the drug is discontinued. Use of the bronchodilator did not influence the long-term decline of FEV1.

Administration, Inhalation↗
PubMed1987

Effects of hyperoxia on medullary ECF pH and respiration in chemodenervated cats.

The effects of transitions from air-breathing to hyperoxia (100% O2), and the reverse, on respiration (phrenic activity) and on medullary extracellular fluid (ECF) pH, or hydrogen ion concentration [H+], were studied in 8 anesthetized, paralyzed, vagotomized and glomectomized cats whose end-tidal PCO2 was kept constant. The transition from air to hyperoxia (7 cats) led to a small (1.23 nmol/L [H+], 0.010 pH unit) acidic shift of medullary ECF and a 24% increase of neural tidal and minute respiratory activity with no significant change of frequency. Opposite changes of approximately equal magnitude followed the transition from hyperoxia to air (8 cats). We show that the slopes of the respiratory responses to changing ECF [H+] in the present study are not different than the slopes with CO2-induced changes of ECF [H+] in 25 other cats. Our findings indicate that most, if not all, of the respiratory increase after hyperoxia is due to accumulation of CO2 and H+ in medullary ECF that act on the central chemoreceptors. We suggest that decreased medullary blood flow and the Haldane effect are the main mechanisms causing the rise of medullary PCO2 and stimulation of breathing.

Animals↗
PubMed1987

Dynamics of medullary hydrogen ion and respiratory responses to square-wave change of arterial carbon dioxide in cats.

1. The dynamics of changes of medullary extracellular fluid (ECF) hydrogen ion concentration ([H+]) and respiration, measured as integrated phrenic nerve activity, were determined in anaesthetized, paralysed, vagotomized and glomectomized cats. ECF [H+] was measured directly by means of a small (2 mm diameter) glass pH electrode placed on the ventral surface of the medulla. The variables were measured continuously after a step change of arterial PCO2 produced by abruptly starting or stopping an infusion of hypercapnic fluid into the aortic arch. 2. Alteration of pH in the descending thoracic aorta at the onset or offset of infusion was complete within 1.5 s after the change began, indicating that it was nearly square wave in form. 3. In sixteen experiments, ECF [H+] began to fall within 2 s of offset of infusion, reflecting aortic-medullary circulation time. Thereafter, ECF [H+] decreased to a stable level over the next 5 min; the curve describing the decrease consisted of two exponential functions, one with a time constant (tau) of 9.5 +/- 0.6 s and a second with a tau of 53 +/- 3 s. 4. We interpret the findings at the offset of CO2 infusion in terms of CO2 wash-out from the medullary ECF. The slow function is associated with wash-out during stable medullary blood flow that develops after 1 min. The early fast function is associated with the decreasing medullary blood flow that occurs during the first minute after change from arterial hypercapnia to normocapnia. 5. We have estimated medullary blood flow using a mathematical model incorporating the two functions. The values obtained are consistent with those in the literature where other methods have been used. Changes of blood flow following the step change of CO2 are fairly rapid, half of the response occurring in 13 s. 6. The change of respiratory activity lags the change of stimulus expressed by [H+], throughout the recovery period and respiration requires up to 8 min to reach a stable level. We attribute this slow response to slow central neural respiratory dynamics, the respiratory after-discharge.

Action Potentials↗
PubMed1987

NHLBI workshop summary. Respiratory disorders of sleep. Pathophysiology, clinical implications, and therapeutic approaches.

The extensive investigation into complex interactions of breathing and sleep have produced answers to numerous important questions, but it is clear that many of the most important questions in this area remain unanswered. Our understanding of the mechanisms through which sleep alters breathing and how disordered breathing can, in turn, effect sleep is rudimentary. Although a large body of recent work has done much to elucidate the factors that act to maintain the patency of the upper airway during sleep, our understanding of such mechanisms and the relative importance of structure and function in this context remains primitive. A better understanding of these issues will be critical in elucidating the pathophysiology of respiratory disorders of sleep. Although some progress has been made in this area, new insights will be critically important to the design of novel, potentially more effective approaches to treatment. Therapeutic decisions are greatly hampered by major uncertainties regarding respiratory disorders of sleep and the clinical significance of symptoms, signs, and laboratory findings, and their relationship to morbidity and mortality. It seems clear that new information regarding the pathophysiology and natural history of these disorders will be important in the development of new, more effective strategies for therapeutic intervention, and this together with rigorous, systematic evaluation of new and future therapeutic approaches will be critical to clinical progress in this field.

Airway Resistance↗
PubMed1987

Diencephalic regulation of respiration and arterial pressure during actual and fictive locomotion in cat.

The purpose of this study was to examine by experimentation the hypothesis that the respiratory and circulatory responses during exercise are attributable to command signals that emanate from the suprapontine brain. We studied the relations between locomotion (exercise) and phrenic nerve activity and arterial pressure in cats that walked or ran on a treadmill and in animals during fictive locomotion, i.e., locomotor activity in motor nerves to legs. Anesthetized cats with intact brains and unanesthetized decorticated cats were used. All preparations exhibited spontaneous actual and fictive locomotion. Electrical stimulation or microinjection of picrotoxin, a GABA antagonist, of the subthalamic locomotor areas always caused locomotion to develop. Phrenic nerve activity and arterial pressure increased in proportion to the level of locomotor activity despite control or ablation of feedback signals from chemoreceptors and vagal receptors. Similar relations were measured during fictive locomotion despite the absence of muscular contraction and limb movement and the lack of change in metabolic rate. These findings provide experimental support for the central command hypothesis for the genesis of the respiratory hyperpnea and increased cardiovascular function that occur during exercise. We believe that the command signals emanate from the subthalamic locomotor area of the diencephalon.

Animals↗
PubMed1986

Resetting of mammalian respiratory rhythm: existence of a phase singularity.

The purpose of this study was to use topological methods of analysis to determine if a phase singularity exists for the neural respiratory oscillator. We studied resetting behavior of central respiratory rhythm, measured as phrenic nerve activity, by using brief stimulations of the superior laryngeal nerve in anesthetized paralyzed adult cats. The strength and timing of stimuli were varied, and the times of onset of subsequent breaths were measured. Two distinct types of phase resetting were identified: type 1 resetting for weak stimuli and type 0 resetting for strong stimuli. With stimuli of intermediate strength, we obtained a series of phase-resetting curves that defined a helicoid-resetting surface having a phase singularity near the transition between late expiration and early inspiration. In this domain resumption of breathing occurred at highly variable resetting times. The mammalian respiratory oscillator thus has qualitative characteristics of response to brief stimuli that are similar to those of other biological oscillators.

Animals↗
PubMed1985

The roles of medullary extracellular and cerebrospinal fluid pH in control of respiration.

To determine the effective stimulus to the central chemoreceptors, we measured CSF and medullary extracellular fluid (ECF) pH and phrenic activity in 11 anesthetized, paralyzed, vagotomized and glomectomized cats. Flat-tipped pH electrodes (2 mm diam.) were used to measure ECF pH on the ventral surface of the medulla and CSF pH 2 mm above the surface. Changes in alveolar/arterial PCO2 were produced by airway occlusions of 10-20 sec durations. Changes in CSF PCO2 and pH were made by infusing 100% CO2 or an acid buffer into the CSF. Airway occlusion caused an increase of alveolar/arterial PCO2. ECF pH began to fall 6-10 sec later, with a maximum decrease of 0.032 pH unit at 21.9 sec. Phrenic activity increased as ECF pH decreased, the greatest activity occurring when ECF pH was most acid. CSF pH decreased after a longer delay. Its maximum decrease at 54.1 sec was smaller (0.026 pH unit) than ECF pH and did not correlate with the increase of phrenic activity. Addition of 100% CO2 or an acid buffer into the CSF produced an acid shift in the CSF pH but no change in ECF pH or phrenic activity. Prolonged (greater than 30 min) increase of acidity of CSF did not alter phrenic activity until ECF pH developed a delayed acid shift. Even then, the change of ECF pH was much smaller than that of CSF. We conclude that medullary chemoreceptors do not respond to changes of CSF pH or PCO2 and that change of pH of CSF minimally affects ECF pH. On the other hand, respiratory responses are closely linked to changes in ECF pH.

Animals↗
PubMed1985

Gas exchange during exercise in hypoxic ducks.

We quantitatively assessed pulmonary gas exchange in Pekin ducks (Anas platyrhynchos) during running exercise (1.44 km X h-1 at 3 degrees incline) while the ducks spontaneously breathed either air (FIO2 = 0.21) or a hypoxic gas mixture (FIO2 = 0.12). During exercise, oxygen consumption increased 3 times above the resting value in normoxia and 3.6 times above rest in hypoxia. The convection requirement rose 34% and 20% in running normoxic and hypoxic ducks, respectively. The O2 extraction coefficient was the same in resting normoxic and hypoxic ducks (0.19 vs 0.18) and decreased by the same amount under exercise conditions (0.14 vs 0.15). Arterial PO2 was maintained during exercise in normoxia but increased slightly during exercise in hypoxia. Cardiac output increased by 73% and 111% during exercise in normoxic and hypoxic ducks, respectively. Calculations indicate that both the O2-diffusing capacity and the total conductance for O2 of the gas exchange system increased markedly during exercise in normoxia and hypoxia. We conclude that at this level of exercise, there was no apparent limitation to gas exchange in either the normoxic or hypoxic Pekin duck.

Acid-Base Equilibrium↗