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Biomedical subjects

A Van Muylem

Publications and source records attributed to A Van Muylem.

At least 19 recordsLinked to original sources

Involvement of peripheral airways during methacholine-induced bronchoconstriction after lung transplantation.

Previous studies have shown that the presence of nonspecific bronchial hyperreactivity (NSBHR) in transplanted subjects is associated with the development of bronchiolitis obliterans, which suggests that NSBHR in these subjects may involve the peripheral airways. We investigated this question by studying the effects of methacholine on the distribution of ventilation using single-breath washouts in 15 heart-lung transplant recipients; 17 nontransplanted subjects with NSBHR were studied for comparison. All subjects had normal baseline lung function, and seven transplanted subjects displayed NSBHR. Methacholine induced a similar decline in FEV1 and specific airway conductance in the two groups. In contrast, whereas methacholine produced similar increases in the slope of the alveolar plateau for SF6 (SSF6) and He (SHe) in the nontransplanted subjects, it always produced greater increases in SHe than SSF6 in the transplanted subjects. This suggests that in the latter, methacholine-induced bronchoconstriction made the distribution of ventilation more heterogeneous in peripheral airways. This involvement of small airways may help in understanding why assessing bronchial reactivity in transplanted subjects provides information on the presence of a pathologic process affecting the bronchioles, and hence on the risk of progression to bronchiolitis obliterans.

Adolescent↗

Bronchiolitis obliterans syndrome in heart-lung transplant recipients: diagnosis with expiratory CT.

PURPOSE: To determine the test performance and longitudinal evolution of air trapping for diagnosing bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Over 7 years, 111 combined inspiratory and expiratory computed tomographic examinations were performed in eight healthy control subjects and 38 heart-lung transplant recipients. Functional impairment was assessed with the BOS classification. Receiver operating characteristic (ROC) analysis was performed to determine the optimal threshold of air trapping to distinguish between patients with and those without BOS and to compute sensitivity and specificity for diagnosing BOS. RESULTS: The extent of air trapping increased with BOS severity (P =.001). A threshold of 32% of air trapping is optimal for distinguishing between patients with and those without BOS and provides a sensitivity of 83%, a specificity of 89%, and an accuracy of 88%. The prevalence of BOS and positive predictive value of air trapping increased with postoperative time, but the negative predictive value of air trapping remained high throughout the study. Patients without BOS who had air trapping exceeding 32% of the parenchyma were at significantly increased risk of developing BOS (P =.004). CONCLUSION: At the threshold of 32%, air trapping is sensitive, specific, and accurate for diagnosing BOS. Patients with air trapping below 32% are unlikely to have BOS. Air trapping exceeding 32% may be an early indicator of future BOS.

Adult↗

Overall and peripheral inhomogeneity of ventilation in patients with stable cystic fibrosis.

We studied distribution of ventilation in patients with cystic fibrosis (CF) who had not had an exacerbation for some time. Patients performed either the vital capacity nitrogen (N(2)) single-breath washout test (VC test) or a modified single-breath washout consisting of 1 L inspired from functional residual capacity (FRC test) of 90% oxygen (O(2)), 5% helium (He), and 5% sulfur hexafluoride (SF(6)). We computed the slopes of phase III of N(2) concentration from the VC test (S(N2) (VC)) and the phase III slopes of the He (S(He)): The SF(6) (S(SF6)), and curves from the FRC test. S(N2) (VC) may be regarded as an index of overall ventilation and the difference (S(SF6) - S(He)) as an index of peripheral ventilation. Three groups were studied: CF, 28 CF patients (8-36 years of age); normal controls (NC), 33 normal nonsmokers (9-55 years of age); and a smoking group (SG), 42 non-CF smoking patients (39-79 years of age). Compared to the NC group, S(N2) (VC) is increased in the CF group, reflecting an overall ventilation impairment. There is no difference in S(N2) (VC) between the CF group and the SG group, suggesting that S(N2), though sensitive, is nonspecific. Compared to both NC and SG groups, (S(SF6) - S(He)) is decreased in the CF group, being on the average negative. This may imply that there is a peripheral impairment in the distribution of ventilation that originates in terminal and respiratory bronchioles. Negative (S(SF6) - S(He)) is statistically associated with the youngest CF patients, suggesting that terminal and respiratory bronchiolar involvement is linked to early stages of the disease. In older CF patients, (S(SF6) - S(He)) is more often positive, suggesting that even more distal airways, such as alveolar ducts, become involved in peripheral inhomogeneity of ventilation.

Adolescent↗

Detection of obliterative bronchiolitis after lung transplantation by indexes of ventilation distribution.

Obliterative bronchiolitis (OB) is the first cause of death of long-term survivors of lung transplantation. The diagnosis is based on pathology and/or on an irreversible decrease in forced expiratory volume in 1 s (FEV(1)) below 80% of the best postoperative value. We tested whether indexes of ventilation distribution may provide evidence of OB before conventional pulmonary function tests (PFTs). Fifty-seven patients with heart-lung (n = 47) or double-lung (n = 10) transplantation were monitored with conventional PFTs and measurements of the slope of the alveolar plateau for He (S(He)), SF(6) (S(SF6)), and N(2) (S(N2)) obtained during single-breath washouts. The date at which a functional variable showed an irreversible change outside the 97.5% confidence interval was compared with the date at which a greater than 20% fall in FEV(1) was observed. A total of 1,929 tests (median, 30 tests per patient) were performed during the 1,215 d (range, 164-2,829 d) of follow-up. Eighteen patients showed an irreversible and greater than 20% fall in FEV(1) during the course of the study. This alteration was preceded by a rise in S(He) in 17 patients and by a rise in S(N2) in 16 patients, which indicated a more heterogeneous ventilation. The median time interval between the change in S(He) and S(N2) and the 20% decrease in FEV(1) was 356 and 168 d, respectively, with seven patients showing an interval of 18 mo or more. Conventional PFTs, including midexpiratory flow rates, deteriorated after indexes of ventilation distribution. Thirty-nine patients did not show any significant and irreversible alteration in conventional PFTs over the study period; only seven of these patients developed significant alterations in ventilation distribution. We conclude that measurements of ventilation distribution detect posttransplant OB much earlier than conventional PFTs.

Adult↗

Evidence of acinar airway involvement in asthma.

We investigated acinar airway involvement in 20 patients with stable asthma, using the phase III slope analysis of the multiple breath N2 washout previously applied in a group of patients with COPD (Am. J. Respir. Crit. Care Med. 1998;157:1573-1577). This technique quantifies severity of conductive and acinar components of ventilation maldistribution separately, through indices S(cond) and S(acin), which increase when respective ventilation inhomogeneities increase. We also investigated the effect of salbutamol inhalation on S(cond) and S(acin) in patients with asthma and compared it with that obtained in patients with COPD. Baseline measurements in the patients with asthma show that (1) acinar ventilation inhomogeneity was indeed abnormal in patients with asthma (S(acin) = 0.195 +/- 0.026 L-1) despite the normal diffusing capacity in this group; S(acin) values were intermediate between those obtained in unaffected individuals and patients with COPD, and that (2) conductive ventilation inhomogeneity was abnormal in the patients with asthma (S(cond) = 0.076 +/- 0.006 L-1) but similar to that obtained in the patients with COPD. Measurements after salbutamol inhalations showed significant changes in S(cond) and S(acin) only in the patients with asthma (p < 0.001). This study primarily demonstrated significant, but partially reversible, acinar airway impairment in patients with asthma, as compared with the more severe baseline acinar airway impairment in patients with COPD, which was not reversible after salbutamol inhalation.

Adult↗

Effects of abdominal strapping on forced expiration in tetraplegic patients.

Patients with traumatic transection of the lower segments of the cervical cord contract the clavicular portion of the pectoralis major during forced expiration and cough, and the rise in intrathoracic pressure resulting from this contraction produces dynamic airway compression in many patients. Because the abdominal muscles are paralyzed, however, there is paradoxical expansion of the abdomen, which may reduce the rise in intrathoracic pressure and the degree of airway collapse. To evaluate the magnitude of this effect, we measured expiratory flow rate (Vexp) and esophageal pressure (Pes) during a series of forced expiratory vital capacity maneuvers and constructed isovolume-pressure flow (IVPF) curves before and after abdominal strapping in eight C5-8 tetraplegic subjects. Strapping produced small and inconsistent changes in maximal Vexp and Pes and resulted in the development of small flow plateaus in only four patients. In tetraplegic subjects, abdominal strapping thus has small effects on forced expiration and is unlikely, therefore, to improve the efficiency of cough.

Abdominal Muscles↗

Conductive and acinar lung-zone contributions to ventilation inhomogeneity in COPD.

We investigated ventilation inhomogeneity in patients with chronic obstructive pulmonary disease (COPD) through use of the multiple breath N2 washout test (MBW). From an alveolar slope analysis throughout the MBW, we derived two indices, S(cond) and S(acin), as a measure of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively (J. Appl. Physiol. 1997;83:1807-1816). We evaluated the relationship of S(cond) and S(acin) to standard lung-function indices by means of a principal-components factor analysis, which linked correlated indices to independent factors accounting for 81% of the total variance within the COPD group. S(acin) was linked to the so-called acinar lung-zone factor, which also comprises diffusion capacity measurements. S(cond) was linked to the so-called conductive lung-zone factor, which also comprises specific airway conductance (S(Gaw)) and forced expiratory flows. FEV1 divided by FVC (FEV1/FVC) was the only variable linked to both the conductive and the acinar lung-zone factors. The fact that S(cond) and S(acin) were linked to independent factors provides statistical confirmation of the hypothesis that S(cond) and S(acin) reflect independent lung alterations, whereas FEV1/FVC behavior indicates a combined conductive and acinar contribution to airways obstruction.

Airway Resistance↗

Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation.

BACKGROUND: Lung function is altered by infection and rejection in patients who undergo heart-lung transplantation. The sensitivity, specificity, and positive/negative predictive values (PPV and NPV) of lung function for the detection of allograft dysfunction in these patients were measured. METHODS: Thirty three patients who underwent heart-lung transplantation were followed for a mean period of 16.3 months. On 123 occasions functional measurements were obtained at the time a transbronchial biopsy specimen and/or bronchoalveolar lavage fluid was taken, which were used as gold standards. Optimal sensitivity (the value for which sensitivity equals specificity) was computed for each functional test from receiver-operator characteristic (ROC) curves. RESULTS: Acute rejection was present on 31 occasions and infection on 36 occasions; 56 samples were normal. Infection and rejection were accompanied by airflow obstruction, a rise in the slopes of the alveolar plateaus for nitrogen, hexafluoride sulphur and helium (SN2, SSF6, and SHe), and a decrease in the difference between SSF6 and SHe (delta S), total lung capacity (TLC), and lung transfer factor (TLCO). Optimal sensitivities for SHe, mid forced expiratory flow (FEF25-75), TLC, and forced expiratory volume in one second (FEV1) were 68%, 67%, 66%, and 60%, respectively; they were not different for infection and rejection and did not change over the study period. For infection and rejection together, PPV ranged from 72% to 88% and NPV from 27% to 52% according to the functional test and the postoperative period considered. CONCLUSIONS: Indices of ventilation distribution, FEF25-75, and TLC have the best optimal sensitivity for the diagnosis of infection and rejection after heart-lung transplantation. The high PPV of pulmonary function in detecting allograft dysfunction observed in this study suggests that a diagnostic procedure should be performed whenever one or more functional tests deteriorate; conversely, the low NPV indicates that a stable pulmonary function does not rule out allograft dysfunction.

Adolescent↗

Ventilation distribution during histamine provocation.

We investigated ventilation inhomogeneity during provocation with inhaled histamine in 20 asymptomatic nonsmoking subjects. We used N2 multiple-breath washout (MBW) to derive parameters Scond and Sacin as a measurement of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively. A 20% decrease of forced expiratory volume in 1 s (FEV1) was used to distinguish responders from nonresponders. In the responder group, average FEV1 decreased by 26%, whereas Scond increased by 390% with no significant change in Sacin. In the nonresponder group, FEV1 decreased by 11%, whereas Scond increased by 198% with no significant Sacin change. Despite the absence of change in Sacin during provocation, baseline Sacin was significantly larger in the responder vs. the nonresponder group. The main findings of our study are that during provocation large ventilation inhomogeneities occur, that the small airways affected by the provocation process are situated proximal to the acinar zone where the diffusion front stands, and that, in addition to overall decrease in airway caliber, there is inhomogeneous narrowing of parallel airways.

Airway Resistance↗

Structural change of the acinus during growth assessed by single-breath tracer gas washouts.

In the present investigation we wanted to study the functional and structural development of the acinus, using a vital capacity (VC) single-breath tracer gas washout test, modified so that the subject inspired helium (He) and sulfurhexafluoride (SF6) in oxygen. We used as indices of ventilation the slopes of N2 (SN2), He (SHe), and SF6 (SSF6) as well as (SSF6-SHe), which may be considered an index of acinar mixing linked to acinar structure. We studied two populations: Population I-49 children and adolescents (8-18 years of age); and Population II-18 non-smoking adults (22-48 years of age). Age and vital capacity (VC) were correlated in Population I, but not in Population II. In both populations there was a significant decrease of SN2, SSF6, and SHe as a function of VC. Growth and VC changes were determinants of these decreases in Population I, while only changes in VC were significant determinants in Population II. For each gas, the regression lines of slope versus VC for Populations I and II were not significantly different; we therefore suggest that the decrease in slope in Population I is mainly due to an increase in lung volume during growth. (SSF6-SHe) was not correlated with VC in Population I and was negatively correlated with VC in Population II (P < 0.01). This discrepancy implies that a child will have a smaller (SSF6-SHe) than an adult at comparable VC. Since the magnitude of (SSF6-SHe) values are related to acinar branching asymmetry, our results suggest that asymmetry of the acinus increases with lung growth and maturation.

Adolescent↗

Evaluation of nocturnal bronchoconstriction by all night tracheal sound monitoring.

BACKGROUND: A study was undertaken to evaluate the reliability of a digital tracheal sound analyser (ELENS-DSA) in predicting nocturnal changes in airways resistance in asthmatic patients. This device allows continuous measurement of the proportion of the time occupied by wheezing (Wh%). METHODS: Nocturnal polygraphic studies with simultaneous continuous monitoring of tracheal sounds and airways resistance were performed in seven patients with nocturnal asthma. In order to evaluate the possible bias in wheezing estimation, each tracheal sound recording was passed through the automatic analyser and simultaneously monitored with earphones by an experienced observer. RESULTS: The device detected audible wheezing with an optimal sensitivity and specificity of 70%. Snoring was a minor cause of the relatively poor characteristics of the system. A close correlation (p < 0.001) between Wh% and airways resistance was observed only in those patients with the highest increase in resistance; when the results of all the subjects were pooled the correlation observed was poor. The predictive value of Wh% in detecting changes in airways resistance during 10 minute intervals was lower than 70%. The positive and negative predictive values of Wh% were raised to 79% and 83%, respectively, for 30 minute intervals. CONCLUSIONS: The ELENS-DSA system is a relatively crude means of detecting wheezing and assessing bronchoconstriction quantitatively. However, it is able to detect accurately nocturnal bronchoconstriction for 30 minute intervals. This finding, along with the fact that the monitoring is non-invasive, suggests that it may be a promising tool, especially for patients during sleep.

Adult↗

Multiple-breath washout and washin experiments in steers.

Multiple-breath N2 washouts (WO) and washins (WI) were performed during regular tidal breathing in 11 unsedated healthy steers approaching pulmonary functional maturity (mean body weight = 271 kg). They inspired 20% O2 in 80% Ar during the WO and air during the WI. For each steer, we computed two indexes of ventilation inhomogeneity from the N2 WO curves: 1) the curvilinearity of the logarithm of end-tidal N2 concentrations as a function of cumulative expired volume reflected in the ratio of two slopes fitted between 100 and 50% and between 50 and 10%, respectively, of end-tidal N2 concentration of the first breath of the WO; and 2) the N2 phase III slope divided by the mean expired concentration (Sn) of each breath also plotted as a function of cumulative expired volume. Equivalent computation of both parameters was done on WI and WO curves, and similar results were obtained. The mean slope ratio was 0.812 +/- 0.119 (SD) for all the steers, which is consistent with topographic gravity-dependent specific ventilation distribution inhomogeneity. Sn was independent of the breath number both for WO and WI (mean Sn = 0.130 +/- 0.057 liters-1), suggesting that emptying between unequally ventilated units, is synchronous. This behavior resembles that observed in rats postmortem (S. Verbanck, E.R. Weibel, and M. Paiva. J. Appl Physiol. 71: 847-854, 1991) but contrasts with experiments in humans, in whom convection-dependent ventilation inhomogeneities generate a marked increase in Sn throughout the entire WO (A. B. H. Crawford, M. Makowska, M. Paiva, and L. A. Engel. J. Appl. Physiol. 59: 838-846, 1985). This is surprising because one would expect gravity-dependent sequential emptying in animals of this size.

Animals↗

Effects of increased +Gz on chest wall mechanics in humans.

We studied the effects of head-to-foot acceleration (+Gz) on chest wall mechanics in five normal subjects seated in a human centrifuge. Results were compared with those previously obtained in the same subjects in microgravity during parabolic flights. In all subjects, end-expiratory abdominal pressure (Pga) and volume (Vab) increased with Gz. On average, end-expiratory Pga increased from 7.4 +/- 1.7 cmH2O at + 1 Gz to 14.9 +/- 2.8 cmH2O at + 3 Gz and end-expiratory Vab increased by 0.32 +/- 0.06 liter between + 1 and + 3 Gz. On the other hand, the abdominal contribution to tidal volume (Vab/VT) and abdominal compliance decreased from 34.7 +/- 5.9% and 52 +/- 6 ml/cmH2O at + 1 Gz to 29.3 +/- 5.1% and 26 +/- 4 ml/cmH2O at + 3 Gz, respectively. Changes in end-expiratory Pga were linear between 0 and + 3 Gz, but changes in end-expiratory Vab, Vab/VT, and abdominal compliance were greater in microgravity than in hypergravity. In contrast to weightlessness, which did not alter minute ventilation and tidal changes in Pga and transdiaphragmatic pressure, these variables increased with increasing Gz. These results indicate that, although changes in Gz have a linear effect on abdominal transmural pressure, hypergravity and weightlessness do not have symmetrical effects on chest wall mechanics.

Abdomen↗

Inert gas single-breath washout after heart-lung transplantation.

We prospectively studied the distribution of ventilation in 22 heart-lung transplant (HLT) recipients. At entry into study, the patients had undergone surgery an average of 6.7 mo earlier, and were followed for a mean period of 16 mo. Vital-capacity (VC) single-breath washouts as well as single-breath washouts using a 1-L inspiration from FRC were performed on a total of 395 occasions. The inhaled gas mixture consisted of 5% He, 5% SF6, and 90% O2, and the expired N2, He, and SF6 concentrations were analyzed. Six patients showed normal standard pulmonary-function tests and indexes of ventilation distribution throughout the study. Five patients gradually developed an irreversible airflow obstruction, presumably due to obliterative bronchiolitis (OB). They showed increases in the slopes of the N2, SF6, and He alveolar plateaus (SN2, SSF6, S(He)), but because S(He) increased more than SSF6, the slope difference (SSF6-S(He)) invariably decreased and became negative in four of five patients. Thirteen patients developed 16 episodes of reversible airflow obstruction as a result of acute infection or rejection of the lung allograft. The alterations in ventilation distribution were qualitatively similar to those seen in patients with OB. We conclude that: (1) ventilation distribution in the lung periphery is normal in HLT recipients with adequate allograft function; (2) the airflow obstruction elicited by OB and acute episodes of lung infection or rejection is accompanied by increases in SN2, SSF6, and S(He) and decreases in SSF6-(He)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evidence of dynamic airway compression during cough in tetraplegic patients.

Although all the well-recognized muscles of expiration are paralyzed after traumatic transection of the lower cervical cord, tetraplegic subjects can still empty their lungs actively by contracting the clavicular portion of the pectoralis major. It is not known, however, whether contraction of this muscle bundle may raise pleural pressure enough to cause dynamic compression of the intrathoracic airways, which is critical for the production of an effective cough. To investigate this question, we measured expiratory flow rate and esophageal pressure during a series of forced expiratory vital capacity (VC) maneuvers in twelve subjects with C5-8 traumatic tetraplegia and constructed isovolume-pressure flow (IVPF) curves. The curves were interpretable with certainty in nine patients. Three of them did not show any plateau of flow. On the other hand, six patients had clearcut plateaus of flow on all IVPF curves between 80-60 and 20% VC, suggesting they had dynamic airway compression. Videoendoscopic recordings in two patients confirmed trachea and main bronchi collapse during forced expiration and cough. We conclude, therefore, that contraction of the pectoralis major causes dynamic airway compression during expiratory efforts in a substantial proportion of tetraplegic subjects. Increasing the pressure-generating capacity of this muscle might thus improve the effectiveness of cough and reduce the prevalence of bronchopulmonary infections.

Adult↗

Rib cage shape and motion in microgravity.

We studied the effect of microgravity (0 Gz) on the anteroposterior diameters of the upper (URC-AP) and lower (LRC-AP) rib cage, the transverse diameter of the lower rib cage (LRC-TR), and the xiphipubic distance and on the electromyographic (EMG) activity of the scalene and parasternal intercostal muscles in five normal subjects breathing quietly in the seated posture. Gastric pressure was also recorded in four subjects. At 0 Gz, end-expiratory LRC-AP and xiphipubic distance increased but LRC-TR invariably decreased, as did end-expiratory gastric pressure. No consistent effect was observed on tidal LRC-TR and xiphipubic displacements, but tidal changes in URC-AP and LRC-AP were reduced. Although scalene and parasternal phasic inspiratory EMG activity tended to decrease at 0 Gz, both muscle groups demonstrated an increase in tonic activity. We conclude that during brief periods of weightlessness 1) the rib cage at end expiration is displaced in the cranial direction and adopts a more circular shape, 2) the tidal expansion of the ventral rib cage is reduced, particularly in its upper portion, and 3) the scalenes and parasternal intercostals generally show a decrease in phasic inspiratory EMG activity and an increase in tonic activity.

Electromyography↗

Inert gas single-breath washout and structural alteration of respiratory bronchioles.

With the perspective of establishing a link between a respiratory function test and alterations of membranous bronchioles, respiratory bronchioles, and alveolar ducts, we performed forced expirations and four kinds of single-breath washout maneuvers on 27 men due to undergo a lobectomy for peripheral bronchial carcinoma. For the single-breath washouts, the inhaled gas mixture consisted of 90% O2, 5% He, 5% SF6. The four maneuvers were the standard vital capacity test and three successive inhalations of 0.5, 1, and 1.5 L from functional residual capacity. The slopes of N2, He, and SF6 for each maneuver were computed, as well as a new index (I2) describing the relative decrease of the difference between the SF6 and the He slopes induced by a larger inspiratory volume. The histologic analysis focused on pigmentation, inflammation, and fibrosis of membranous bronchioles, respiratory bronchioles, and alveolar ducts. There was a linear relationship with a highly significant correlation coefficient between the new index I2 and the degree of inflammatory (r = 0.73) and fibrotic (r = 0.63) changes of the respiratory bronchioles; this correlation persisted in patients with a normal FEV1/VC ratio. These preliminary data open the way to finding a test for early peripheral (intraacinar) airway dysfunction.

Adult↗