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Biomedical subjects

M G Cosio

Publications and source records attributed to M G Cosio.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

Cellularity of the alveolar walls in smokers and its relation to alveolar destruction. Functional implications.

Inflammatory cells are believed to play an important role in the pathogenesis of emphysema; however, a relationship between presence of cells in the lung parenchyma and its destruction has never been shown. The aim of this study was to quantitate alveolar septal cellularity in smokers' lungs and to investigate its relationship with parenchymal destruction and lung function. The lungs of 23 smokers (SS) undergoing thoracotomy for localized pulmonary lesions were compared with those of eight nonsmokers (NS) and five smokers (AS) who died suddenly of nonrespiratory causes. Pulmonary function tests were performed within 1 wk of surgery in SS. For each subject, we quantitated alveolar wall cells (CELLS), an index of alveolar wall destruction (DI), and the mean linear intercept (Lm). As no significant differences were found between S and AS with regard to these indices, we combined them (Group S) for comparison with NS. Although Lm was not significantly different between S and NS, (0.331 +/- 0.072 versus 0.288 +/- 0.038), CELLS and DI were higher in S than in NS (48 +/- 8 versus 25 +/- 2 cells/mm, p less than 0.001; 47 +/- 20 versus 17 +/- 5, p less than 0.001, respectively). Further, CELLS and DI were significantly correlated (r = 0.799, p less than 0.001). The number of polymorphonuclear cells (PMN) in S can exceed that in NS by as much as 5-fold; however, PMN were inversely correlated with parenchymal destruction (DI) (r = 0.598, p less than 0.01). Thus, smokers' lungs have alveolar septal hypercellularity, possibly inflammatory, and closely related to destruction involving cells other than the PMN.

Aged

Pulmonary denervation in humans. Effects on dyspnea and ventilatory pattern during exercise.

The role of the pulmonary autonomic nerves in the mediation of respiratory sensation is unclear. Pulmonary neurogenic mechanisms may contribute to dyspnea either directly or indirectly via an influence on the pattern of ventilation. Using human heart-lung transplantation as a model of pulmonary denervation, we studied the ventilatory response, respiratory drive (P0.1), and sensation of breathlessness (modified Borg scale) during maximal incremental bicycle exercise. The subjects were four female heart-lung transplant recipients 3 to 9 months post-transplant and 10 age-matched control subjects. The ventilatory response to increasing CO2 output (VCO2) was higher (p less than 0.001) in transplant recipients than in control subjects, such that ventilation at peak exercise was similar in the two groups despite a lower peak VCO2 in transplant recipients. The ratio of tidal volume to inspiratory capacity increased with increasing ventilation in a similar fashion in both groups. Although the respiratory rate increased more quickly in transplant recipients, it was similar at peak ventilation in the two groups. Ventilatory timing and duty cycle at half-peak and peak ventilation were similar in transplant recipients and control subjects. Dyspnea ratings were not different between the two groups at similar levels of ventilation. Dyspnea as a function of P0.1 was also similar in transplant and control groups. These results indicate that pulmonary neurogenic mechanisms play a role in determining the level, but not the pattern, of ventilation during exercise. Furthermore, these pathways do not appear to contribute significantly to the perception of breathlessness in normal humans.

Adult

Effect of saline infusion on body temperature and endurance during heavy exercise.

We tested the hypothesis that volume infusion during strenuous exercise, by expanding blood volume, would allow better skin blood flow and better temperature homeostasis and thereby improve endurance time. Nine males exercised to exhaustion at 84.0 +/- 3.14% (SE) of maximum O2 consumption on a cycle ergometer in a double-blind randomized protocol with either no infusion (control) or an infusion of 0.9% NaCl (mean vol 1,280.3 +/- 107.3 ml). Blood samples and expired gases (breath-by-breath), as well as core and skin temperatures, were analyzed. Plasma volume decreased less during exercise with the infusion at 15 min (-13.7 +/- 1.4% control vs. -5.3 +/- 1.7% infusion, P less than 0.05) and at exhaustion (-13.6 +/- 1.2% vs. -1.3 +/- 2.2%, P less than 0.01). The improved fluid homeostasis was associated with a lower core temperature during exercise (39.0 +/- 0.2 degrees C for control and 38.5 +/- 0.2 degrees C for infusion at exhaustion, P less than 0.01) and lower heart rate (194.1 +/- 3.9 beats/min for control and 186.0 +/- 5.1 beats/min for infusion at exhaustion, P less than 0.05). However, endurance time did not differ between control and infusion (21.96 +/- 3.56 and 20.82 +/- 2.63 min, respectively), and neither did [H+], peak O2 uptake, and CO2 production, end-tidal partial pressure of CO2, blood lactate, or blood pressure. In conclusion, saline infusion increases heat dissipation and lowers core temperature during strenuous exercise but does not influence endurance time.

Adolescent

Pressure-volume curves in smokers. Comparison with alpha-1-antitrypsin deficiency.

The diagnosis of emphysema has been associated with changes in the appearance of the pressure-volume (P-V) curve: reduced maximal recoil pressure, increased lung volume, and a shift in the position of the curve to the left. In our clinical practice, we have observed that patients with chronic obstructive lung disease (COPD) commonly had P-V curves with reduced maximal elastic recoil that are difficult to classify according to the classic description of the P-V curve in emphysema. In order to study the variability of P-V curves, we studied 39 cigarette smokers attending a pulmonary clinic (age, 61 +/- 1 yr; smoking history, 45 +/- 3 pack-years; mean +/- SEM) and compared them with 20 patients with alpha-1-antitrypsin deficiency (AATD) (age, 41 +/- 2 yr; 13 smokers with a smoking history of 17 +/- 2 pack-years, and seven nonsmokers). Subjects underwent spirometry, lung volume, and diffusing capacity measurements as well as static deflation P-V curves. To characterize the P-V curves, we used transpulmonary pressure at 90% of TLC (PL90) as a measure of overall recoil and specific compliance (Csp) as a measure of the slope of the initial part of the P-V curve. The curves of non-AATD smokers were classified into three groups: 13 had PL90 greater than or equal to 80% predicted (Group I), 13 had PL90 less than 80% predicted and Csp greater than or equal to 0.08 (Group II), and 13 had PL90 less than 80% predicted and Csp less than 0.08 (Group III).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Reversibility of upper airway obstruction after levodopa therapy in Parkinson's disease.

Serial flow-volume loops obtained in a 66-year-old patient with Parkinson's disease and recurrent episodes of dyspnea revealed a pattern consistent with upper airway obstruction, reversible after oral intake of levodopa. This observation shows that extrapyramidal involvement of the striated upper airway musculature may limit airflow and cause respiratory symptoms. Persistence of flow oscillations on the flow-volume loop contour after reversal of upper airway obstruction and dyspnea should be considered to reflect upper airway dysfunction with possibly serious consequences.

Aged

Mucus hypersecretion and viscoelasticity changes in cigarette-smoking dogs.

Chronic cigarette smoke exposure is well known to cause mucus hypersecretion in experimental animals, but the alterations in mucus rheology have not been described. We studied mucus hypersecretion and viscoelasticity changes in nine tracheostomized beagle dogs exposed to cigarette smoke. The dogs were trained to stand quietly in a harness, and smoke was delivered via a cuffed tracheostomy tube. A 35-cm3 bolus was introduced to the inspiratory line each 20 s, using unfiltered 70-mm cigarettes (20 mg tar, 1.2 mg nicotine). Each dog smoked 10 cigarettes per day over 2.5 h, 5 days per week. Two dogs were exposed for 6 months; 7 dogs were exposed for 10 months. Five dogs served as sham-smoking controls. Mucus was collected twice weekly without drugs by resting a cytology brush on the lower trachea for 2-5 min. The rheological properties of the mucus samples were determined by magnetic rheometry, which yields elasticity and viscosity as a function of frequency. The mucus was also weighed, and the galactose content was determined by phenolsulfuric acid assay. The mucus collection rate served as an index of tracheal mucus flux, and the galactose assay as a marker of mucous glycoprotein content. The tracheal mucus linear velocity (TMV) was determined periodically under xylazine analgesia by observing charcoal particle transport bronchoscopically. Eight of 9 smoking dogs developed mucus hypersecretion (flux greater than 2 X control) versus 1 of 5 controls (p less than .01). TMV did not change significantly in 10 months of exposure. In the first 2-4 months of smoking, the elasticity and viscosity of the mucus both decreased (mean at 4 months = 42% control, p less than .001), as did the galactose content (mean at 4 months = 48% control, p less than .01). At this stage, according to model studies, the mucus should have been more easily clearable by ciliary action. After 6 months, the viscoelasticity returned toward the initial control level, while the galactose content remained low, suggesting an alteration in the nature of the mucous glycoprotein.

Animals