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Biomedical subjects

G Peces-Barba

Publications and source records attributed to G Peces-Barba.

At least 19 recordsLinked to original sources

Increased collagen deposition correlated with lung destruction in human emphysema.

BACKGROUND: To study the relationship between collagen amount and degree of emphysema as assessed by mean linear intercept (Lm) and correlating these with lung function test workup in patients with and without COPD. METHODS: Lung function tests were assessed in 16 smokers or ex-smokers and 1 non-smoker in order to separate them into two groups: COPD (FEV1/FVC lower than 70%) and non-COPD. A piece of lung tissue was used to analyse the collagen amount (HYP) by means of a colorimetric method. Morphometry was assessed to divide patients into two groups according to Lm: Lm > 260 micrometers was considered non-emphysema and Lm < 260 mm mild-emphysema. RESULTS: The non-emphysema group had a mean Lm value of 246.08+/-3.12 micrometers and the mild-emphysema group of 276.29+/-4.26 micrometers. The amount of hydroxyproline was significantly higher in the mild-emphysema group than in the non-emphysema group (7.82+/-0.67 vs. 5.50+/-0.54 microgram/g tissue). There was a clear positive correlation between Lm and HYP (r=0.55) and a negative correlation between Lm and DlCO (R=-0.5092). No correlation was found between the functional test and HYP, nor were there significant differences between COPD and non-COPD patients for Lm and HYP. CONCLUSIONS: Emphysema is associated with collagen deposition in the lungs, and air space size correlates with the amount of lung collagen even when there is no emphysema.

Aged↗

Effect of pulmonary perfusion on the slopes of single-breath test of CO2.

The objective of this study was to evaluate the effects of lung perfusion on the slopes of phases II (S(II)) and III (S(III)) of a single-breath test of CO(2) (SBT-CO(2)). Fourteen patients submitted to cardiac surgery were studied during weaning from cardiopulmonary bypass (CPB). Pump flow was decreased in 20% steps, from 100% (total CPB = 2.5 l.min(-1).m(-2)) to 0%. This maneuver resulted in a progressive and opposite increase in pulmonary blood flow (PBF) while maintaining ventilator settings constant. SBT-CO(2), respiratory, and hemodynamic variables remained unchanged before and after CPB, reflecting a constant condition at those stages. S(III) was similar before and after CPB (19.6 +/- 2.8 and 18.7 +/- 2.1 mmHg/l, respectively). S(III) was lowest during 20% PBF (8.6 +/- 1.9 mmHg/l) and increased in proportion to PBF until exit from CPB (15.6 +/- 2.2 mmHg/l; P < 0.05). Similarly, S(II) and the CO(2) area under the curve increased from 163 +/- 41 mmHg/l and 4.7 +/- 0.6 ml, respectively, at 20% PBF to 313 +/- 32 mmHg/l and 7.9 +/- 0.6 ml (P < 0.05) at CPB end. When S(II) and S(III) were normalized by the mean percent expired CO(2), they remained unchanged during the protocol. In summary, the changes in PBF affect the slopes of the SBT-CO(2). Normalizing S(II) and S(III) eliminated the effect of changes in the magnitude of PBF on the shape of the SBT-CO(2) curve.

Aged↗

Lower pulmonary diffusing capacity in the prone vs. supine posture.

We evaluated the effect of prone positioning on gas-transfer characteristics in normal human subjects. Single-breath (SB) and rebreathing (RB) maneuvers were employed to assess carbon monoxide diffusing capacity (DlCO), its components related to capillary blood volume (Vc) and membrane diffusing capacity (Dm), pulmonary tissue volume (Vti), and cardiac output (Qc). Alveolar volume (Va) was significantly greater prone than supine, irrespective of the test maneuver used. Nevertheless, Dl(CO) was consistently lower prone than supine, a difference that was enhanced when appropriately corrected for the higher Va prone. When adequately corrected for Va, diffusing capacity significantly decreased by 8% from supine to prone [SB: Dl(CO,corr) supine vs. prone: 32.6 +/- 2.3 (SE) vs. 30.0 +/- 2 ml x min(-1) x mmHg(-1) stpd; RB: Dl(CO,corr) supine vs. prone: 30.2 +/- 2.2 (SE) vs. 27.8 +/- 2.0 ml x min(-1) x mmHg(-1) stpd]. Both Vc and Dm showed a tendency to decrease from supine to prone, but neither reached significance. Finally, there were no significant differences in Vti or Qc between supine and prone. We interpret the lower diffusing capacity of the healthy lung in the prone posture based on the relatively larger space occupied by the heart in the dependent lung zones, leaving less space for zone 3 capillaries, and on the relatively lower position of the heart, leaving the zone 3 capillaries less engorged.

Adult↗

Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema.

Hyperpolarised gases have been most recently used in magnetic resonance imaging to demonstrate new image-derived pulmonary function parameters. One of these parameters is the apparent diffusion coefficient, which reflects the sizes of the structures that compartmentalise gas within the lung (i.e. alveolar space). In the present study, noninvasive parameters were compared to microscopic measurements (mean linear intercept and mean alveolar internal area). Nonselective helium-3 gas density coronal ex vivo images and apparent diffusion maps were acquired in control and elastase-induced panacinar emphysema rats. Total lung capacity was considered the reference for both imaging experiments and lung fixation. A mild degree of emphysema was found based on mean linear intercept (134 +/- 25 microm) versus control (85 +/- 14 microm). The apparent diffusion coefficients were significantly different between the two groups (0.18 +/- 0.02 and 0.15 +/- 0.01 cm2 x s(-1) for elastase and control, respectively). A significant correlation between the apparent diffusion coefficient and corresponding morphometric parameters in mild emphysema was demonstrated for the first time. This study opens the possibility of estimating absolute airspace size using noninvasive techniques.

Animals↗

[Non-invasive ventilation in patients with severe hypercapnic encephalopathy in a conventional hospital ward].

OBJECTIVE: To report our experience with non-invasive ventilation (NIV) at two levels of pressure (Bi-PAP) on a general respiratory medicine ward with patients in hypercapnic impaired consciousness and/or coma who had not previously been in an intensive care unit (ICU). METHODS: This was a prospective study of 13 patients, mean age 81 years (65-96), treated with NIV through a face mask. Ten had chronic obstructive pulmonary disease, with a mean FEV1 in stable condition of 35.2 14.6%. Glasgow scores upon admission were >/= 7. Arterial gases were monitored until suspension of NIV. RESULTS: After NIV for a mean 19 5 h/day in the first 48 hours and later of 6 1 h/day until a total of 74 9 h, 9 patients (69%) survived. The mean initial pH for these patients was 7.17 0.028 and the mean initial pCO2 was 101 9 mm Hg. In 7 cases (78%), coma was reversed in the first 48 h and a significant improvement in pH was observed in the 12-24 h analysis. Mean pH upon discharge was 7.44 0.013 and mean pCO2 was 54 2.8 mmHg. Four patients died, even though their initial or subsequent arterial gases at 12-24 h were not significantly different from those of the survivors. CONCLUSION: NIV on a general respiratory medicine ward can offer an alternative to oro-tracheal intubation for patients with hypercapnic impaired consciousness and/or coma who do not meet the criteria for admission to the ICU.

Acute Disease↗

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.

Adult↗

Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea syndrome.

The aim of this trial was to evaluate the effectiveness of continuous positive airway pressure (CPAP) in patients with mild sleep apnea- hypopnea syndrome (SAHS). One hundred forty-two consecutive patients with mild SAHS (apnea-hypopnea index 10-30, without severe sleepiness) were randomly assigned to receive conservative treatment (CT)-sleep hygiene and weight loss-(65 patients) or CT plus CPAP (77 patients), and 125 patients (86% males, age: 54 +/- 9 yr, BMI: 29 +/- 4 kg/m(2), AHI: 20 +/- 6, ESS: 12 +/- 4) completed the follow-up. The following outcomes were assessed at inclusion and after 3 and 6 mo of treatment: sleepiness (Epworth scale, multiple sleep latency test [MSLT]), other symptoms related to SAHS, cognitive function, and perceived health status (Functional Outcomes of Sleep Questionnaire [FOSQ], Nottingham Health profile). The relief of SAHS-related clinical symptoms was significantly greater in the CPAP group than in the CT group; the Epworth scale and FOSQ also showed more improvement in the CPAP group but did not reach significance. There were no significant differences in the other tests performed probably because the baseline values were normal. CPAP compliance was 4.8 +/- 2.2 h and treatment continuation was accepted by 62% of the patients at the end of the study. These results suggest that CPAP can be considered in treating patients with mild SAHS on the basis of an improvement in symptoms.

Chi-Square Distribution↗

Single-breath washouts in a rotating stretcher.

Vital capacity single-breath washouts using 90% O2-5% He-5% SF6 as a test gas mixture were performed with subjects sitting on a stool (upright) or recumbent on a stretcher (prone, supine, lateral left, lateral right, with or without rotation at end of inhalation). On the basis of the combinations of supine and prone maneuvers, gravity-dependent contributions to N2 phase III slope and N2 phase IV height in the supine posture were estimated at 18% and 68%, respectively. Whereas both He and SF6 slope decreased from supine to prone, the SF6-He slope difference actually increased (P = 0.015). N2 phase III slopes, phase IV heights, and cardiogenic oscillations were smallest in the prone posture, and we observed similarities between the modifications of He and SF6 slopes from upright to prone and from upright to short-term microgravity. These results suggest that phase III slope is partially due to emptying patterns of small units with different ventilation-to-volume ratios, corresponding to acini or groups of acini. Of all body postures under study, the prone position most reduces the inhomogeneities of ventilation during a vital capacity maneuver at both inter- and intraregional levels.

Adult↗

N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats.

This study investigated the effect of cigarette smoke exposure and the potential protection N-acetylcysteine (NAC) in rat lungs. Forty-eight rats were exposed to cigarette smoke (CS) for 10 weeks, without (CS group) or with (CS+NAC group) oral intake of NAC 200 mg x rat(-1) x day(-1), or to fresh air (Control). All rat lungs were assessed in terms of lung function, ventilation distribution (nitrogen, helium and sulphur hexafluoride phase III slopes), and morphometry (airway wall thickening of small, medium and large bronchi). The small bronchi, defined as the airways with an internal perimeter <1,000 microm showed significantly thicker airway walls in the CS than in the Control group. By contrast, no airway wall thickening was observed in the CS+NAC group with respect to Control. Except for decreased lung volumes and compliance in CS and CS+NAC groups, which were entirely attributable to smaller body weight gain, lung function was indistinguishable from Control. Phase III slopes were significantly increased only in the CS group. In conclusion, smoke-induced alterations in the rat lungs were reflected in wall thickening of the small bronchi and increased ventilation maldistribution. These smoke-induced morphometric and ventilation distribution alterations were prevented by N-acetylcysteine.

Acetylcysteine↗

Lung function and ventilation inhomogeneity in rat lungs after allergen challenge.

We studied the early response to ovalbumin challenge in sensitized Brown-Norway rats through its effect on N(2), He, and SF(6) phase III slopes of the single-breath washout and on indexes of lung function. Sensitized rats showed varying degrees of response in terms of pulmonary pressure (PL), with increases ranging between 125 and 225% of baseline. The sensitized rats presented decreased quasistatic compliance, forced vital capacity, and end-expiratory flow, with all three lung function indexes showing a significant negative correlation with corresponding PL values. They also showed significant positive correlations of PL with the N(2), He, and SF(6) phase III slopes, reflecting diffusion-convection-dependent inhomogeneities generated by conformation changes throughout the entire rat lung. In addition, the rats showing the most marked PL increases (>150% baseline PL) also revealed a reversal of the SF(6)-He slope difference because of a more marked SF(6) than He slope increase. This latter finding suggests that the degree of structural heterogeneity during early response is even more marked in the most peripheral rat lung generations.

Allergens↗

Intrapulmonary gas mixing in panacinar- and centriacinar-induced emphysema in rats.

We studied ventilation distribution using the single-breath washout technique in rats with two types of induced emphysema: panacinar-like (by instilled elastase) and centriacinar-like (by inhaled CdCl2 combined with oral intake of beta-aminopropionitrile). Morphologically, panacinar and centriacinar groups presented a similar degree of airspace enlargement, which was irregularly distributed and also accompanied by fibrosis only in the centriacinar group. In terms of mechanical properties, the centriacinar group presented lower end-expiratory flows and lower compliance than the panacinar group. The ventilation distribution patterns were also different between both groups. Single-breath washout phase III slopes, reflecting mainly diffusion-convection-dependent inhomogeneities in rat lungs, were largest in the centriacinar group. The SF6-He slope difference, which was reversed in both emphysema groups with respect to the control group, could be attributed mainly to He slope changes in the panacinar group and to SF6 slope changes in the centriacinar group. In addition, the respective He and SF6 slope decrease as a function of end-inspiratory breath-hold time, was only different from the control group in the centriacinar group. The observed ventilation distribution patterns can be explained by interacinar elastic changes in the panacinar group and severe interacinar structural alterations in the centriacinar group.

Administration, Inhalation↗

Effect on single-breath washout and lung function of elastase-induced emphysema in rats.

Lung volumes, diffusing capacity (DLCO), quasi-static pressure-volume curves (P-V), forced expiration (FE) and He-SF6 single-breath washout (SBW) were performed in Wistar rats with emphysema induced by different doses of pancreatic elastase in saline, instilled intratracheally 6 wk prior to the tests. Emphysema was quantitatively assessed by mean linear intercept (Lm) measurements on 5-microns lung sections. Lung volume, P-V curve, and FE dependence on Lm, as well as the nonsignificant dependence of DLCO on Lm, are generally similar to results reported by others. The most interesting observation concerns the SBW: N2 slopes of the alveolar plateau, compared for identical lung volumes, did not change with the degree of emphysema. By contrast, the He-SF6 slope difference did depend significantly on the degree of emphysema. Based on the diffusion front theory, the present work suggests that in rats with elastase-induced emphysema, the phase III slope modifications relate mainly to elastic and not to structural alterations.

Analysis of Variance↗

Multiple-breath washout experiments in rat lungs.

Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2-5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.

Animals↗

Single-breath washout experiments in rat lungs.

Single-breath washouts were performed on 30 Wistar rats postmortem in studies in which breaths of 90% O2-5% He-5% SF6 were given. We investigated the effects of variations in preinspiratory lung volume, inspired volume, end-inspiratory breath-hold time, and inspiratory and expiratory flows on the alveolar plateau slopes for N2, He, and SF6. The main result is that the slope for He was always larger than the slope for SF6, except for large breath-hold times (approximately 15 s), contrary to previous findings in other species. Slopes for the three gases decreased with increasing inspiratory and expiratory flows when flows were greater than 1 ml/s. There was a strong correlation between the magnitude of a slope and its curvilinearity, suggesting that the concentration heterogeneity in the lung that causes the slope is due to interaction between diffusion and convection. The results seem incompatible with heterogeneities of parenchymal elasticity, which have been said to contribute to alveolar slopes in dog lungs but appear to be completely explainable as the result of diffusion-convection interaction in an asymmetric lung structure that has acini widely spread along the tracheobronchial tree.

Animals↗

Effects of inspiratory and expiratory time and high mouth pressures on calculated DLCO by the single-breath procedure. Results with different methods to measure the effective breath-holding time.

We have studied the influence of several manoeuvres modifying inspiratory and expiratory flow, with and without an external obstruction, on measured single-breath diffusing capacity (DLCO). By this method, we could evaluate the effects of increased inspiration or expiration time, independently of the influence of high (negative or positive) mouth pressures. Ten tests were performed in each of 11 trained normal subjects. The sequence of repeated manoeuvres was as follows: (1) basal; (2) inspiratory obstruction (IO); (3) expiratory obstruction (EO); (4) slow inspiration without obstruction (SI), and (5), slow expiration without obstruction (SE). A second, inverted sequence was then performed. The obstructive manoeuvres were forced by a unidirectional valve with a circular hole of 5 mm in diameter. Mouth pressures were registered. The slow flows were voluntarily controlled to be similar to the corresponding flows during the obstructive manoeuvre (approximately 15% of each vital capacity/second). Determinations of breath-holding time (tBH) were calculated by the methods of Jones-Meade, Ogilvie and the American Epidemiology Standardization Project (ESP), but using the same expiratory sample. We found that (DLCO) obtained with the three methods were statistically different (p less than 0.0001) from each other for all manoeuvres. Regarding the basal manoeuvre, there were statistical differences (p less than 0.01) with SI on the Jones-Meade, with IO on the ESP and with SI and IO on the Ogilvie timing methods. Between IO and SI, statistical differences (p less than 0.01) were observed in the three methods, but there was no statistical difference between SE and EO by any method.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

A simple method of correcting diffusing capacity for alveolar volume reduction in restrictive lung diseases.

We studied the discriminative power of the transfer factor (TLCO), KCO (TLCO/Va) and ZCO (a corrected TLCO according to alveolar volume measured (Va), introduced by our group), in order to differentiate diffuse interstitial disease from other restrictive diseases. Measurements were taken in 46 subjects, divided into two groups: Pure restriction (group 1: normal subjects with voluntary restriction and diseased subjects) and (2) diffuse interstitial restriction (group 2). There were no statistical differences in Va between groups 1 and 2. TLCO was statistically lower in groups 1 and 2 in comparison with the control group (normal values of our laboratory in test with Va greater than 90% of predicted) and showed a significant difference when group 1 was compared with group 2. Similar results (but with higher values than those of the control group) were found for KCO. A similar difference exists in ZCO only when group 2 is compared with group 1, but not when group 1 is compared with the control group. The corrected diffusion capacity ZCO yields the highest discriminative power.

Humans↗