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Biomedical subjects

M G Cosio

Publications and source records attributed to M G Cosio.

At least 37 records · Page 2Linked to original sources
PubMed1995

Overview of the pathology of emphysema in humans.

In summary, emphysema in smokers should not be considered a single entity with predictable clinical and functional abnormalities. Decreases in flow are the ultimate abnormalities seen in COPD with emphysema; however, the pathophysiology of the flow alterations are vastly different in CLE and PLE. Based on the present understanding of emphysema, it could be predicted that the short-term results of pneumonectomy might produce some improvement in flows in CLE but not in PLE. Any improvement, however, may be short-lived, because the new mechanical conditions resulting from the removal of emphysematous lung would destroy the remaining lung at an accelerated rate, thus returning to the prior emphysematous state.

Bronchi↗
PubMed1994

Mechanisms of apnea termination in obstructive sleep apnea. Role of chemoreceptor and mechanoreceptor stimuli.

Previous work from our laboratory has indicated that mechanoreceptor feedback from the respiratory muscles may play an important role in arousal and apnea termination in obstructive sleep apnea (OSA). Other studies have pointed to a prominent role for chemoreceptor stimuli. We postulated that mechanoreceptor stimuli from the respiratory system are the primary determinant of apnea termination, and that chemoreceptor stimuli exert their effect indirectly through stimulation of ventilation and thus proprioceptive feedback. To test this, we measured the diaphragmatic tension-time index (TTdi) during obstructive sleep apneas in seven male subjects with severe untreated OSA. We compared the maximal TTdi values at end-apnea during administration of air, O2, and CO2. We reasoned that if mechanoreceptor stimuli mediate apnea termination, changing the degree of chemoreceptor stimulation during apneas should not alter the level of respiratory effort at end-apnea. O2 administration produced a significant increase in end-apneic arterial oxygen saturation (SaO2) and increased apnea duration. CO2 administration led to an increase in pre- and postapneic end-tidal carbon dioxide pressure (PETCO2), and tended to shorten apneas. However, the mean value for maximal end-apneic TTdi was 0.12 +/- 0.01 (SEM) during room air breathing and was unaltered by O2 (0.12 +/- 0.01) or CO2 (0.11 +/- 0.01) administration. The consistency of end-apneic TTdi values despite the varying chemical drive supports the hypothesis that apnea termination in OSA is mediated by mechanoreceptor feedback from the respiratory system, most likely from the respiratory muscles. The influence of chemoreceptor information may be mediated indirectly through an effect on ventilatory effort.

Adult↗
PubMed1994

Extent of centrilobular and panacinar emphysema in smokers' lungs: pathological and mechanical implications.

In order to quantify the extent of centrilobular (CLE) and panacinar (PLE) emphysema and the degree of the possible overlap between the two forms in smokers, the lungs of 25 smokers undergoing lung resection for peripheral lung tumours were studied. The extent of CLE and PLE was assessed by point counting, and the lungs were classified as having pure CLE (C, n = 5), predominant CLE with areas of PLE (CP, n = 7), predominant PLE with features of CLE (PC, n = 7), and pure PLE (P, n = 6) according to the percentage of lung involved by either form. Preoperative pulmonary function tests and the score of inflammation and the diameters of the small airways were also measured. Mean linear intercept (Lm), a measure of mean interalveolar wall distances and forced expiratory volume in one second (FEV1) were similar in the four groups. Small airway pathology was a predominant feature in lungs with CLE, and was significantly decreased in a stepwise fashion as the amount of PLE increased. This was especially so for the amount of muscle in the airway wall and the diameters of the airways. By contrast, lung compliance was higher in panacinar than in centrilobular emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Morphological and cellular basis for airflow limitation in smokers.

Airflow limitation has two well-defined components, increased resistance, which is found predominantly in the small airways, and loss of elastic recoil. Small airways contribute to the increased resistance to flow by the narrowing of the airway lumen. Morphometric studies have shown that smokers have increased epithelial abnormalities, cellular inflammatory infiltrates in the airway wall, increased muscle and fibrosis, when compared with nonsmokers. Along with these anatomical changes, an increased percentage of airways < 400 microns in diameter is found. In addition to the measured changes, other nonmeasurable, dynamic events occur in the airways of smokers, which further decrease lumen diameter. There is ample evidence to show that the airways of smokers react to nonspecific stimuli by constricting, which results in increased resistance and decreased forced expiratory volume in one second (FEV1). The pathological changes found in smokers, that could be responsible for active muscle constriction and airway narrowing include: 1) airway epithelial damage, resulting in increased permeability and impairment of other epithelial function; 2) chronic airway inflammation; 3) structural changes in the airway wall; and 4) loss of alveolar attachments. However, not all smokers develop the abovementioned airway abnormalities. We describe how smokers could develop either centrilobular emphysema (CLE), or panlobular emphysema (PLE). We have found that smokers with CLE have more abnormal and narrower small airways, and flow limitation is correlated with the small airway abnormalities and not with loss of recoil. In contrast, smokers with PLE have much less severe airway abnormalities, diffuse emphysema that can be detected microscopically at a stage when FEV1 might be only mildly abnormal, and early changes in elastic recoil as evidenced by the changes in the pressure-volume curve of the lung. Furthermore, in PLE, airflow limitation is correlated with loss of recoil but not with abnormalities in the small airways. We believe that the mechanisms involved in the pathogenesis of the two types of emphysema in smokers are different; an airborne mechanism for CLE, possibly related to airway hyperresponsiveness, and a bloodborne mechanism for PLE, which may be related to dysfunction of alpha 1-antiproteases. We conclude that the separation of smokers based on their emphysema type is essential if we are to understand the pathogenesis of chronic obstructive pulmonary disease (COPD) in these subjects.

Bronchi↗
PubMed1994

Changes in obstructive sleep apnea characteristics through the night.

It was our impression that the respiratory parameters in obstructive sleep apnea (OSA) worsened as the night progressed. To confirm this, we review polysomnographic studies from 66 patients with apnea-hypopnea indices (AHI) of 40 to 125 events per hour, dividing bed time into equal quartiles. As the night progressed, the mean apnea duration (MAD) increased from 27.2 s to 34.6 s (p < 0.0001), mainly from increases during NREM sleep. The proportion of time spent in apnea increased from 54 to 71% (p < 0.0001) due to increases in both MAD and the proportion of REM sleep (from 2.8 to 14.7% of the total sleep time). The AHI did not change significantly between quartiles. Even though preapneic oxygen saturation did not change and apnea duration increased as the night progressed, the end-apneic saturation did not decrease, hence the rate of oxygen desaturation decreased. Also, it was found that patients with an AHI greater than 65 events per hour increased their proportion of time spent in apnea significantly more than those with an AHI smaller than 65, as the night progressed. In the patients with an AHI greater than 85, this was due to both an increase in MAD and AHI. In conclusion, in patients with an AHI greater than 40 events per hour, the severity of apnea increased as the night progressed due to lengthening of MAD, increased proportion of REM sleep, and in the most severe patients, also an increase in AHI. Even though the exact pathophysiologic mechanisms for the observed changes are unknown, a decrease in respiratory muscle effort with consequent decrease in oxygen consumption may explain both the lengthening of the apneas and the decrease in the rate of oxygen desaturation.

Apnea↗
PubMed1994

Quality adjusted life years added by treatment of obstructive sleep apnea.

We assessed the impact of treatment with nasal continuous positive airway pressure (nCPAP) on the quality of life of 19 patients with obstructive sleep apnea (OSA). We measured the utility for the patients' health states before and with treatment using the standard gamble approach. The study group had an average age of 57 years and had been on treatment for a mean of 9.5 months. For all the patients, the polysomnographic indicators of OSA disease severity improved markedly with treatment. For nine of the 12 symptoms most commonly associated with OSA, the patients reported improvement during treatment. The mean utility and the standard deviation obtained with the standard gamble method were 0.87 +/- 0.17 on treatment and 0.63 +/- 0.29 pretreatment. The difference in utility between treatment and pretreatment health states was combined with the life expectancy of each patient to generate the number of quality adjusted life years (QALYs) considered equivalent to the impact of treatment. This resulted in an average gain of 5.4 QALYs. When we related this impact to the cost of treatment, we obtained a cost-utility ratio between Can $3,397 and Can $9,792 per QALY added. These costs are relatively small when compared to the cost per QALY for many other clinical interventions. Hence, nCPAP clearly offers the prospect for a well-tolerated therapy with a very favorable cost-utility ratio.

Adult↗
PubMed1993

Relationship of resting lung mechanics and exercise pattern of breathing in patients with chronic obstructive lung disease.

To investigate the influence of resting pulmonary mechanics on the pattern of breathing during exercise in chronic obstructive pulmonary disease (COPD), we studied 29 patients with moderate to severe COPD (FEV1 50 +/- 20 percent predicted), and 10 normal subjects. Lung mechanics were studied using esophageal balloon technique and body-box. Incremental exercise testing was performed to exhaustion. As minute ventilation (VE) increases, COPD patients with the highest pulmonary resistance (RI) or lowest elastic recoil pressure (PL), used a greater tidal volume/vital capacity ratio (VT/VC) than the COPD patients with more normal RL or lowest PL. To describe the breathing pattern during exercise, an exponential constant (K) describes the rates of increase in VT/VC ratio with increasing VE, calculated according to the equation VT = VC(1-e-KVE). The K values achieved by COPD patients were higher than in normal subjects. In addition, K value correlated negatively with the resting FEV1 and FVC of COPD patients. When COPD patients were grouped according to their K values, it was revealed that patients with high K values generated greater VT/VC ratio and also have the most abnormal resting lung mechanics. These results suggest that the exercise breathing pattern in COPD patients is significantly influenced by the degree of impairment of resting lung mechanics.

Adult↗
PubMed1992

Induction of sleep apnoea with negative pressure ventilation in patients with chronic obstructive lung disease.

BACKGROUND: Negative pressure ventilation provides intermittent non-invasive ventilatory assistance for patients with advanced chronic obstructive lung disease. Upper airway obstruction during sleep, a reported complication of the technique, may, however, limit its clinical applicability. METHODS: The effects of nocturnal negative pressure ventilation on ventilation and on indices of sleep quality were investigated in five patients with severe chronic obstructive lung disease (mean (SE) FEV1 31% (3%) predicted) who had completed three months of nightly negative pressure ventilation. Subjects underwent overnight polysomnography on consecutive nights, the first night serving as a control and negative pressure ventilation being provided on the second night. Ventilators were adjusted to result in maximum suppression of the peak phasic electromyogram signal from the diaphragm. RESULTS: Negative pressure ventilation resulted in substantial increases in episodes of obstructive apnoea and hypopnoea (mean (SE)/h 59.3 (19.8) v 3.2 (1.3) on control nights). Most obstructive events, however, were associated with under 3% oxygen desaturation, and the lowest recorded values for overnight oxygen saturation were similar on the two study nights. Negative pressure ventilation was also associated with significant increases in the frequencies of movement arousals and changes in sleep stage. CONCLUSIONS: Negative pressure ventilation applied during sleep to patients with advanced chronic obstructive lung disease may result in the development of recurrent episodes of apnoea and hypopnoea as well as altered sleep quality, which could limit its clinical applicability.

Aged↗
PubMed1992

Exertional dyspnea and ventilation in hyperthyroidism.

Dyspnea is recognized to be an important feature in patients with hyperthyroidism at rest and during exercise. However, its etiology is not well-understood. Since dyspnea is thought to be related to the perception of excessive ventilatory effort, we explored the possibility that dyspnea in these patients might be related to an inappropriate ventilatory response to the increased metabolic rate. We studied 11 hyperthyroid patients and 11 age- and sex-matched controls, performing spirometry, lung volumes, mouth pressure measurements, and incremental exercise test. Central drive was estimated by measuring P0.1 and sensation of dyspnea by the Borg scale. We found that hyperthyroid patients (1) have higher ventilation than normal subjects during exercise even when corrected for VCO2 levels; (2) this increased ventilation is secondary to increased central drive which is correlated to the T3ria level (r = 0.85, p less than 0.01); (3) hyperthyroid patients are more dyspneic than controls; and (4) the increased drive can be normalized by beta-blockade. We conclude that the main ventilatory abnormality in hyperthyroid patients is an inappropriate increase in respiratory drive, possibly secondary to increased adrenergic stimulation.

Adult↗
PubMed1991

Clinical features and treatment of obstructive sleep apnea.

OBJECTIVE: To review the clinical features and treatment of obstructive sleep apnea (OSA). DATA SOURCE AND SELECTION: All articles on OSA published in French and English between 1970 and 1990 and indexed in Index Medicus were reviewed. Studies addressing the epidemiologic features and clinical aspects of OSA were selected, and special emphasis was given to articles reporting the effects of treatment on morbidity and mortality rates. MAIN RESULTS: OSA is characterized by episodes of upper airway obstruction during sleep that result in repetitive hypoxemia and sleep disruption. OSA leads to various neuropsychologic and cardiovascular complications, including daytime hypersomnolence, cognitive impairment, systemic and pulmonary hypertension and cardiac arrhythmias. There is suggestive evidence that the death rate among affected people is increased. The true incidence of OSA is unknown, but estimates have varied from 1% upwards among men. The current treatment with the greatest overall effectiveness and acceptability is nasal continuous positive airway pressure. CONCLUSION: This common, readily treatable disorder is associated with serious complications and therefore must be widely recognized by health professionals.

Arrhythmias, Cardiac↗
PubMed1991

Nasal continuous positive airway pressure facilitates respiratory muscle function during sleep in severe chronic obstructive pulmonary disease.

Patients with chronic respiratory insufficiency due to severe chronic obstructive pulmonary disease (COPD) and presumed respiratory muscle fatigue may benefit from therapeutic maneuvers aimed at reducing the magnitude of inspiratory muscle effort. Recent work has demonstrated that continuous positive airway pressure (CPAP) can significantly reduce inspiratory effort and work of breathing in COPD patients with acute respiratory failure. Accordingly it was reasoned that prolonged CPAP administration may similarly reduce the work of breathing in stable COPD patients with chronic respiratory insufficiency, thereby allowing recovery from respiratory muscle fatigue. The purpose of this study was to determine the feasibility of employing nasal CPAP during sleep as a means of implementing this approach to reducing inspiratory muscle effort in such patients. Standard polysomnographic parameters were recorded during nocturnal administration of nasal CPAP in eight stable patients with severe COPD (FEV1 = 26.7 +/- 3.9% of predicted). Esophageal pressure, diaphragmatic (EMGdi) and parasternal intercostal (EMGic) electromyographic activity, arterial oxyhemoglobin saturation (SaO2), and transcutaneous PCO2 (PtcCO2) were also measured. Breathing pattern was determined by respiratory inductive plethysmography. In each patient an optimum level of nasal CPAP could be determined that produced consistent reductions in indices of inspiratory muscle effort without changing tidal volume or breathing frequency. Highly significant reductions in the tidal excursions of esophageal pressure and the pressure-time integral for the inspiratory muscles occurred at the optimum CPAP level in all patients. EMGdi and EMGic were similarly reduced. SaO2 and PtcCO2 were unaffected by CPAP. These results indicate that nasal CPAP can effectively reduce inspiratory muscle effort during sleep in patients with severe COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

The destructive index and early lung destruction in smokers.

The destructive index (DI), a measure of alveolar septal damage and emphysema, has been proposed as a sensitive index of lung destruction that closely reflects functional abnormalities, especially loss of elastic recoil. To better understand the progression of lung destruction in smokers, we studied the contribution of its principal components: breaks in the alveolar septa (DIb) and the presence of emphysematous spaces (DIe), and compared them to the mean linear intercept (Lm) and DI as originally described. To do this we employed lungs obtained at autopsy from non-smokers and smokers. Lungs were selected by emphysema score (ES) so that all cases were emphysema free (nonsmokers and seven smokers) or had minimal emphysema (nine smokers; ES = 5). Of these indices, only DIb was significantly increased in the lungs of smokers: 17.8 +/- 1.2 versus 12.4 +/- 1.6, p less than 0.05. We also investigated the regional distribution of destruction by comparing results in upper and lower lobes. DIe, but not DIb, was significantly increased in upper lobes of smokers. These data support the notion that increases in DI in the lungs of smokers that occur before increases in Lm or ES reflect the presence of alveolar septal breaks and highlight the importance of alveolar septal destruction as a precursor to the development of airspace enlargement in the lungs of cigarette smokers.

Adult↗
PubMed1991

Obstructive sleep apnea during pregnancy. Therapy and implications for fetal health.

A 32 yr-old woman in her last trimester of pregnancy was found to have severe obstructive sleep apnea (OSA). The overnight polysomnogram demonstrated an apnea plus hypopnea index of 159 events per hour. Apneas were associated with severe oxygen desaturation to 40% during rapid eye movement sleep, maternal bradycardia, and second degree heart block. External cardiotocography showed normal fetal heart rate reactivity to fetal movements, even during the apneas and episodes of oxygen desaturation. Nasal continuous positive airway pressure at a level of 15 cm H2O effectively treated the apneas and desaturation and had no effect on the fetal heart rate. The patient was induced electively during the 39th wk of pregnancy and gave birth to a newborn with growth retardation. Early recognition and treatment of OSA in pregnancy might prevent problems with fetal development.

Adult↗
PubMed1991

Centrilobular and panlobular emphysema in smokers. Two distinct morphologic and functional entities.

In order to investigate the hypothesis that different morphologic patterns of disease might correspond to different mechanical properties of the lung in emphysema, pulmonary function tests and lung mechanics were measured in 34 subjects undergoing lung resection for peripheral lung tumors. Using standard microscopic criteria, pure or predominant centrilobular (n = 18) or panlobular (n = 16) emphysema was diagnosed in lungs. The degree of emphysema measured by the mean linear intercept (Lm) was not significantly different between the two groups. However, the coefficient of variation of the interalveolar wall distance (CV) was significantly higher for the same Lm in CLE than in PLE. This indicates that CLE has an uneven pattern of destruction, whereas PLE is more homogeneous. CLE had a higher degree of abnormalities in the small airways (SAD) than did PLE (p less than 0.05) mainly because of significantly higher muscle score (p less than 0.001) and fibrosis. CLE also had a higher proportion of airways less than 400 microns in diameter than did PLE (p less than 0.05). Static compliance, specific compliance, and the exponential constant (K) were significantly lower (p less than 0.005, p less than 0.001, and p less than 0.05, respectively) in CLE than in PLE. FEV1/FVC was significantly correlated with SAD in CLE (r = -0.69, p less than 0.01) but not in PLE (r = 0.29 p greater than 0.05); conversely, FEV1/FVC was significantly correlated with elasticity (K) in PLE (r = -0.72, p less than 0.01) but not in CLE (r = 0.08, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Subclinical cardiac dysfunction in sarcoidosis.

Clinically apparent myocardial disease is infrequent in sarcoidosis. However, autopsy data show myocardial involvement in up to 30 percent of patients. Unexplained exertional symptomatology is a common complaint in patients with sarcoidosis. In this study, we investigated whether abnormal cardiac function might limit exercise performance in patients with sarcoidosis without overt cardiac involvement. We studied exercise responses in 35 patients with sarcoidosis and compared them with 28 untrained controls. Seventy-seven percent of the patients were symptomatic. Pulmonary function test results were lower in the group with sarcoidosis than normal controls, but they were within normal range. Only one patient had evidence of ventilatory limitation to exercise. Sixteen (46 percent) patients had abnormally increased heart rates (HRs) at rest prior to exercise testing and/or with exercise. Rapid HRs were confirmed during daily activities by continuous ambulatory electrocardiographic (ECG) monitoring. Left ventricular ejection fraction (LVEF) was measured to determine if systolic dysfunction could account for abnormal HR responses. Of patients with abnormally increased HRs, five had LVEFs less than 50 percent, and eight had normal LVEFs, of whom 75 percent had tachycardia at rest. Retrospective comparison of HR responses and LVEF between patients who did or did not receive corticosteroids revealed no significant differences between groups. We conclude that abnormal HR responses in patients without evident cardiac sarcoidosis are common and exertional symptoms in this population are often associated with chronotropic abnormalities. The exact mechanisms underlying the chronotropic abnormalities are unclear, but they likely include ventricular systolic dysfunction, sinus node dysfunction from granulomatous infiltration, or combinations of the two.

Adult↗
PubMed1990

Behavior of morphometric indices in pancreatic elastase-induced emphysema in rats.

Two morphometric indices, the destructive index (DI), a measure of alveolar wall destruction, and the proportion of destroyed alveolar attachments to the airways (AA), have been proposed as measures of early lung destruction in human smokers. The aim of this study was to compare DI and AA to the usual measure of airspace enlargement--the mean linear intercept (Lm)--in experimental emphysema. Porcine pancreatic elastase was administered intratracheally to 2 groups of Brown Norway rats (high-dose, n = 8, 1 IU/g body weight; low-dose, n = 4, 0.7 IU/g; control, n = 7). Total lung capacity (TLC), functional residual capacity (FRC) and pressure-volume curves were measured 3 weeks after administration of elastase. Lung elasticity was assessed by chord compliance (Cst). Administration of high-dose, but not low-dose, elastase led to significant increases in FRC and TLC. Cst significantly increased after high-dose elastase compared to controls (p less than 0.01). Lm increased after both low-dose and high-dose elastase compared to controls (p less than 0.01); DI and AA were increased only after high-dose elastase. Significant correlations were found between each morphometric index and Cst; the highest correlation was with AA. Behavior of the morphometric indices in this model differed from that reported in human smokers: Lm was a more sensitive measure of destruction than DI, reflecting a process marked by predominance of airspace enlargement over alveolar septal breaks. These differences from human smokers may result from a differing underlying pathogenesis of lung destruction.

Analysis of Variance↗
PubMed1990

Intravenous bicarbonate and sodium chloride both prolong endurance during intense cycle ergometer exercise.

To determine the effects of neutralizing exercise systemic acidosis via the intravenous route upon endurance and metabolic responses, eight lean, normal, postabsorptive men exercised to exhaustion at about 80% of their VO2 max (69 +/- 3%, mean +/- SEM, of maximum power output) on a cycle ergometer. Exercise studies were performed either with no infusion (control) or with a total infusion volume of about 1.5 L, mainly as 1.3% sodium bicarbonate or as 0.9% sodium chloride (NaCl), infused (double-blind) throughout exercise. The sodium bicarbonate was to prevent acid-base change, the sodium chloride was as a control for the volume infused. Arterialized venous blood and breath-by-breath analysis of expired gases were obtained. [H+] (nmol.L-1) and [HCO3-] (mmol.L-1) at exhaustion were similar in control and NaCl (46.5 +/- 1.8, 19.9 +/- 0.9), but remained unchanged from rest values with bicarbonate (38.4 +/- 0.9, 24.8 +/- 1.5, p less than 0.005 vs control and NaCl). At exhaustion, VO2, VCO2, RER, heart rate, and systolic BP as well as FFA, glycerol, alanine, insulin, norepinephrine, and epinephrine did not differ among protocols. Endurance was markedly prolonged (p less than 0.01) with bicarbonate (31.9 +/- 5.8 min) and NaCl (31.8 +/- 4.1 min) compared with the control (19.0 +/- 2.9 min) condition. Plasma glucose at exhaustion was higher (p less than 0.025) in the control compared to bicarbonate and NaCl experiments, while lactate was higher (p less than 0.025) in the bicarbonate than in the control and NaCl experiments. Thus, the prolonged endurance with sodium bicarbonate infusion could not be explained either by its effect of maintaining blood acid-base equilibrium or concomitant metabolic changes.

Acid-Base Equilibrium↗