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Manuel Paiva

Publications and source records attributed to Manuel Paiva.

11 recordsLinked to original sources

Small airway function improvement after smoking cessation in smokers without airway obstruction.

OBJECTIVE: Studying smokers with normal spirometry requires monitoring tools of the peripheral lung. A validated multiple breath washout technique was used to assess possible recovery of smoking-induced small airway malfunction in acinar and conductive lung zones. METHODS: Eighty-seven smokers with a smoking history of at least 10 pack-years but absence of spirometric airflow obstruction were invited for assessment of lung function and small airway function at baseline and after 1 wk, 3 mo, 6 mo, and 12 mo of smoking cessation. A control group of 16 persistent smokers was studied at the same time intervals. MEASUREMENTS AND MAIN RESULTS: Of the 87 smokers, 66, 32, 28, and 21% successfully ceased smoking for 1 wk, 3 mo, 6 mo, and 12 mo, respectively. Lung function parameters remained essentially unaffected by smoking cessation. Ventilation heterogeneity showed transient improvements after 1 wk in the acinar lung compartment with a return to baseline afterwards. By contrast, there were persistent improvements in the conductive airway compartment; for example, smokers who successfully quit smoking for 12 mo (n=18) showed a 30 and 42% reduction of conductive airways abnormality after 1 wk and 1 yr, respectively. CONCLUSIONS: Smokers with early signs of small airway malfunction who successfully quit smoking show sustained improvements of conductive airway malfunction. In contrast, acinar airway malfunction quickly returns to baseline after a transient improvement.

Adult↗

The functional benefit of anti-inflammatory aerosols in the lung periphery.

BACKGROUND: The target of anti-inflammatory therapy in asthma is thought to be situated, at least partly, in the lung periphery, and inhaled steroid aerosols are being engineered to reach it. However, the potential effect of such aerosols cannot be fully evaluated by conventional lung function tests because these are insensitive to peripheral lung structure. OBJECTIVE: A prospective cohort study was conducted to investigate whether ultrafine steroid aerosols can elicit a response in the lung periphery, using a validated multibreath washout technique that can distinguish acinar from conductive lung zone function. METHODS: In 30 stable patients with asthma with a wide range of disease severity (FEV(1) 27% to 108% predicted), we assessed conductive and acinar airway function abnormality at baseline, with patients on a standard dry powder steroid aerosol and after switching them to an ultrafine steroid aerosol. RESULTS: Only in those patients with abnormal acinar airway function at baseline (n = 16) did acinar heterogeneity show a consistent improvement after switching to an ultrafine steroid aerosol; the improvement was also correlated with baseline acinar heterogeneity (r = -0.67; P = .007). Although all patients with asthma also presented conductive airway abnormality at baseline, no changes were observed in this lung zone with the switch to the ultrafine aerosol (P > .1). CONCLUSION: Among stable patients with asthma, those with acinar lung zone abnormality at baseline have the potential to receive functional benefit from an ultrafine steroid aerosol. Clinical studies comparing the efficacy of steroid aerosols targeted to the deep lung should at least include a measurement of peripheral lung zone function. CLINICAL IMPLICATIONS: A new noninvasive measure of small airways function reveals why, and for which particular patients with asthma, small steroid aerosol particles can be of therapeutic use.

Adolescent↗

Single-breath test in lateral decubitus reflects function of single lungs grafted for emphysema.

The slope of alveolar plateau for nitrogen derived from the single-breath test is useful to assess the function of bilateral lung grafts, but this technique is not applicable to patients with single-lung grafts due to the confounding influence of the native lung. We tested the hypothesis that the nitrogen slope measured in lateral decubitus with the graft in nondependent position may primarily reflect the distribution of ventilation in this lung. Fifteen patients with single-lung transplantation for emphysema, 10 healthy controls, and 7 patients with advanced emphysema performed single-breath washouts in right and left lateral decubitus; nitrogen slope was measured between 75 and 100% of expired volume. In 10 transplant recipients, the volume of each lung was measured in the two postures by computerized tomography. Nitrogen slope was unaffected by posture in normal controls and emphysema patients. On the other hand, nitrogen slope in transplant recipients was invariably smaller, with the graft in nondependent vs. in dependent position. Values of nitrogen slope with the graft in nondependent position were similar to those obtained in normal controls but significantly smaller than those obtained in emphysema patients. Computerized tomography studies in this position indicated that the volume expired below functional residual capacity was exclusively contributed by the graft. We conclude that, in patients with single-lung transplantation for emphysema, 1) measuring nitrogen slope in lateral decubitus allows to distinguish between the graft and the native lung, and 2) nitrogen slope obtained with the graft in nondependent position reflects ventilation distribution in this lung.

Breath Tests↗

Foreword.

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Animals↗

Anatomically based three-dimensional model of airways to simulate flow and particle transport using computational fluid dynamics.

We have studied gas flow and particle deposition in a realistic three-dimensional (3D) model of the bronchial tree, extending from the trachea to the segmental bronchi (7th airway generation for the most distal ones) using computational fluid dynamics. The model is based on the morphometrical data of Horsfield et al. (Horsfield K, Dart G, Olson DE, Filley GF, and Cumming G. J Appl Physiol 31: 207-217, 1971) and on bronchoscopic and computerized tomography images, which give the spatial 3D orientation of the curved ducts. It incorporates realistic angles of successive branching planes. Steady inspiratory flow varying between 50 and 500 cm(3)/s was simulated, as well as deposition of spherical aerosol particles (1-7 microm diameter, 1 g/cm(3) density). Flow simulations indicated nonfully developed flows in the branches due to their relative short lengths. Velocity flow profiles in the segmental bronchi, taken one diameter downstream of the bifurcation, were distorted compared with the flow in a simple curved tube, and wide patterns of secondary flow fields were observed. Both were due to the asymmetrical 3D configuration of the bifurcating network. Viscous pressure drop in the model was compared with results obtained by Pedley et al. (Pedley TJ, Schroter RC, and Sudlow MF. Respir Physiol 9: 387-405, 1970), which are shown to be a good first approximation. Particle deposition increased with particle size and was minimal for approximately 200 cm(3)/s inspiratory flow, but it was highly heterogeneous for branches of the same generation.

Aerosols↗

Ventilation asymmetry after transplantation for emphysema: role of chest wall and mediastinum.

After single-lung transplantation for emphysema, the hyperinflated native lung and the graft have different extents and rates of inflation and emptying. This requires that breathing produces asymmetrical expansion of the chest wall, displacement of the mediastinum, or both. In a first study in four seated transplant recipients, we measured the volumes of the two hemithoraces with optoelectronic plethysmography. Functional residual capacity and total lung capacity were identical on the native and transplanted sides, and changes in chest wall volume during CO(2)-induced hyperpnea and FVC maneuvers were similar on both sides. Studies with computerized tomography in three of these patients and in four additional patients in supine posture indicated that the mediastinum was shifted toward the graft at functional residual capacity and total lung capacity. The mediastinum moved toward the native lung during tidal and full inspiration and toward the graft during tidal and forced expiration; additional studies with fluoroscopy showed qualitatively similar changes in upright posture. In summary, the two hemithoraces assume identical static volumes and show similar volume changes during CO(2)-induced hyperpnea and FVC maneuvers in patients with single-lung transplantation for emphysema; displacement of the mediastinum accommodates part, if not all, of the unequal lung volumes and asymmetrical ventilation.

Female↗

Noninvasive assessment of airway alterations in smokers: the small airways revisited.

It has been shown that structural changes in small airways of smokers with average smoking histories greater than 35 pack-years could be reflected in the single-breath washout test. The more sophisticated multiple breath washout test (MBW) has the potential to anatomically locate the affected small airways in acinar and conductive lung zones through increased phase III slope indices S(acin) and S(cond), respectively. Pulmonary function, S(acin), and S(cond) were obtained in 63 normal never-smokers and in 169 smokers classified according to smoking history (< 10 pack-years; 10-20 pack-years; 20-30 pack-years; > 30 pack-years). Compared with never-smokers, significant changes in S(acin) (p = 0.02), S(cond) (p < 0.001), and diffusing capacity (DL(CO); p < 0.001) were detected from greater than 10 pack-years onwards. Spirometric abnormality was significant only from greater than 20 pack-years onwards. In smokers with greater than 30 pack-years and DL(CO) less than 60% predicted, the presence of emphysema resulted in disproportionally larger S(acin) than S(cond) increases. We conclude that S(cond) and S(acin) can noninvasively detect airway changes from as early as 10 pack-years onwards, locating the earliest manifestations of smoking-induced small airways alterations around the acinar entrance. In these early stages, the associated DL(CO) decrease may be a reflection of ventilation heterogeneity rather than true parenchymal destruction. In more advanced stages of smoking-induced lung disease, differential patterns of S(acin) and S(cond) are characteristic of the presence of parenchymal destruction in addition to peripheral airways alterations.

Breath Tests↗

Nonreversible conductive airway ventilation heterogeneity in mild asthma.

A multiple-breath washout technique was used to assess residual ventilation heterogeneity in the conductive and acinar lung zones of asthmatic patients after maximal beta(2)-agonist reversibility. Reversibility was assessed in 13 patients on two separate visits corresponding to a different baseline condition in terms of forced expiratory volume in 1 s [FEV(1); average FEV(1) over 2 visits: 92 +/- 21% of predicted (SE)]. On the visit corresponding to each patient's best baseline, 400 micro g salbutamol led to normal acinar ventilation heterogeneity, normal FEV(1), and normal peak expiratory flow; i.e., none was significantly different from that obtained in 13 matched controls. By contrast, conductive ventilation heterogeneity and forced expiratory flow after exhalation of 75% forced vital capacity remained significantly different from controls (P < or = 0.005 on both indexes). In addition, the degree of postdilation conductive ventilation heterogeneity was similar to what was previously obtained in asthmatic individuals with a 19% lower baseline FEV(1) and twofold larger acinar ventilation heterogeneity (Verbanck S, Schuermans D, Noppen M, Van Muylem A, Paiva M, and Vincken W. Am J Respir Crit Care Med 159: 1545-1550, 1999). We conclude that, even in the mildest forms of asthma, the most consistent pattern of non-beta(2)-agonist-reversible ventilatory heterogeneity is in the conductive lung zone, most probably in the small conductive airways.

Adrenergic beta-Agonists↗

Modeling of impact of gas molecular diffusion on nitric oxide expired profile.

Present descriptions of nitric oxide (NO) transport in the lungs use two compartment models: airway compartment without mixing and alveolar compartment with perfect mixing. These models neglect NO molecular diffusion in the airways. To assess the impact of axial diffusion on expired NO profile, we solved a transport equation that incorporated diffusion, convection, and NO sources in the symmetrical Weibel model of the lung. When NO parameters computed from experimental data with the two compartment models are used in our model as NO sources, simulated end-expired NO is 29-45 and 64-78% of experimental values at expiratory flows of 50 and 2,000 ml/s, respectively. These lower values are because of NO axial diffusion: During expiration, NO back diffusion (opposed to convection) prevents some NO from being expired, so a two- to fivefold increase of airway NO excretion is necessary to simulate end-expired NO consistent with experimental data. We conclude that, insofar as a significant amount of NO is produced in small airways, models neglecting NO axial diffusion underestimate excretion in the airways.

Computer Simulation↗

Tidal volume single-breath washin of SF6 and CH4 in transient microgravity.

We performed tidal volume single-breath washins (SBW) by using tracers of different diffusivity and varied the time spent in microgravity (microG) before the start of the tests to look for time-dependent effects. SF(6) and CH(4) phase III slopes decreased by 35 and 26%, respectively, in microG compared with 1 G (P < 0.05), and the slope difference between gases disappeared. There was no effect of time in microG, suggesting that neither the hypergravity period preceding microG nor the time spent in microG affected gas mixing at volumes near functional residual capacity. In previous studies using SF(6) and He (Lauzon A-M, Prisk GK, Elliott AR, Verbanck S, Paiva M, and West JB. J Appl Physiol 82: 859-865, 1997), the vital capacity SBW showed an increase in slope difference between gases in transient microG, the opposite of the decrease in sustained microG. In contrast, tidal volume SBW showed a decrease in slope difference in both microG conditions. Because it is only the behavior of the more diffusive gas that differed between maneuvers and microG conditions, we speculate that, in the previous vital capacity SBW, the hypergravity period preceding the test in transient microG provoked conformational changes at low lung volumes near the acinar entrance.

Adult↗

Internet-based home monitoring of pulmonary function after lung transplantation.

Home monitoring of spirometry has been advocated in lung transplant recipients for the early detection of acute infection and rejection of the allograft. We have developed a user-friendly, Internet-based telemonitoring system providing direct transmission of home spirometry to the hospital. In this prospective study, we assessed patient adherence with the monitoring, agreement between home and hospital spirometry, intrasubject coefficient of variation (CV) for FEV(1) and FEF(25-75), and sensitivity of these variables for the detection of acute complications. Twenty-two bilateral-lung and heart-lung transplant recipients were followed for a median of 473 d (range, 60-822), during which 13,833 measurements were obtained. Patient compliance was 55% for two measurements a day and 84% for one measurement a day. Agreement between home and hospital spirometry was within 4% for FEV(1) and 6% for FEF(25-75). Mean CV was 3.2% for FEV(1) and 7.5% for FEF(25-75). Using transbronchial lung biopsy and/or bronchoalveolar lavage as gold standards, the sensitivity of home spirometry was 63%, and 23% of true positives were detected by changes in FEF(25-75) alone. We conclude that home monitoring of pulmonary function in lung transplant recipients via the Internet is feasible and provides very reproducible data; yet it has only a mild sensitivity for the detection of acute allograft dysfunction.

Adult↗