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Biomedical subjects

L Gagliardi

Publications and source records attributed to L Gagliardi.

At least 19 recordsLinked to original sources

Response of the hypothalamic-pituitary-adrenal axis to small dose arginine-vasopressin and daily urinary free cortisol before and after alprazolam pre-treatment differs in obesity.

OBJECTIVE: Arginine vasopressin (AVP) has a central role in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress conditions. A low dose of AVP has been shown to have a modest, but significant effect on ACTH response in normal weight subjects. The aim of this study was to test the response of the HPA axis in obese subjects in order to assess eventual primary neuroendocrine alterations, previously demonstrated by using AVP combined with corticotropin releasing hormone (CRH). In addition, given its central inhibitory action on the HPA axis, we investigated whether the suppressive capacity of alprazolam (APZ) pretreatment on the hormone response to low-dose AVP challenge and daily urinary free cortisol (UFC) excretion rate may be altered in the presence of obesity. DESIGN: Fifteen overweight or obese women and eight normal-weight controls randomly underwent two low-dose AVP tests (0.3 UI iv bolus), one without (AVP test) and the other preceded by APZ administration (0.5 mg at midnight and 0.5 mg 90 min before the test in the morning at 08:30 h) (APZ/AVP test). Blood samples for ACTH and cortisol assay were obtained at baseline and throughout each test. The day before each test, 24h-UFC/ creatinine was also mea-sured. RESULTS: Basal ACTH levels were similar in the two groups, whereas cortisol concentrations were significantly lower in the overweight/obese group. Overweight/obese women had higher ACTH and cortisol responses to the AVP tests and significantly greater hormone inhibition after APZ than controls. In both groups, AVP-induced delta-peak cortisol values before and after APZ pre-treatment were significantly correlated. Body fat distribution had no effect on the HPA axis response to AVP either before or after APZ. Moreover, APZ decreased 24h-UFC/creatinine values unsignificantly in controls and by approximately 50% in the overweight/obese subjects. These changes were unrelated to the cortisol response to the AVP test before and after APZ pretreatment. On the other hand, percent changes of 24h-UFC/creatinine after APZ were negatively related to the body mass index (BMI) but positively with waist circumference values, which indicates that the abdominal obesity phenotype may counteract the 24 h-UFC/creatinine that would be expected on the basis of BMI values. CONCLUSIONS: Our data further support the concept that in women obesity may represent a condition of hyperresponsiveness or hypersensitivity of the HPA axis to neuroendocrine stimuli, which appear to be independent of feedback control. In addition, the data on the inhibiting capacity of APZ on UFC excretion confirm that the alterations of the HPA axis in obesity is particularly evident in the abdominal phenotype.

Adult↗

Assessing mortality risk in very low birthweight infants: a comparison of CRIB, CRIB-II, and SNAPPE-II.

BACKGROUND: Illness severity scores are increasingly used for risk adjustment in clinical research and quality assessment. Recently, a simplified version of the score for neonatal acute physiology (SNAPPE-II) and a revised clinical risk index for babies (CRIB-II) score have been published. AIM: To compare the discriminatory ability and goodness of fit of CRIB, CRIB-II, and SNAPPE-II in a cohort of neonates < 1500 g birth weight (VLBWI). METHODS: Data from 720 VLBWI, admitted to 12 neonatal units in Lombardy (Northern Italy) participating in a regional network, were analysed. The discriminatory ability of the scores was assessed measuring the area under the receiver operating characteristic curve (AUC). Outcome measure was in-hospital death. RESULTS: CRIB and CRIB-II showed greater discrimination than SNAPPE-II (AUC 0.90 and 0.91 v 0.84, p < 0.0004), partly because of the poor quality of some of the data required for the SNAPPE-II calculation-for example, urine output-but also because of the relative weight given to some items. In addition to each score, several variables significantly influenced survival in logistic regression models. Antenatal steroid prophylaxis, singleton birth, absence of congenital anomalies, and gestational age were independent predictors of survival for all scores, in addition to caesarean section and not being small for gestation (for SNAPPE-II) and a five minute Apgar score of > or = 7 (for SNAPPE-II and CRIB). CONCLUSIONS: CRIB and CRIB-II had greater discriminatory ability than SNAPPE-II. Risk adjustment using all scores is imperfect, and other perinatal factors significantly influence VLBWI survival. CRIB-II seems to be less confounded by these factors.

Epidemiologic Methods↗

A theoretical study of the structure of tricarbonatodioxouranate.

The results of a study on the ground states of tricarbonato complexes of dioxouranate using multiconfigurational second-order perturbation theory (CASSCF/CASPT2) are presented. The equilibrium geometries of the complexes corresponding to uranium in the formal oxidation states VI and V, [UO(2)(CO(3))(3)](4)(-) and [UO(2)(CO(3))(3)],(5)(-) have been fully optimized in D(3)(h)() symmetry at second-order perturbation theory (MBPT2) level of theory in the presence of an aqueous environment modeled by a reaction field Hamiltonian with a spherical cavity. The uranyl fragment has also been optimized at CASSCF/CASPT2, to obtain an estimate of the MBPT2 error. Finally, the effect of distorting the D(3)(h)() symmetry to C(3) has been investigated. This study shows that only minor geometrical rearrangements occur in the one-electron reduction of [UO(2)(CO(3))(3)](4)(-) to [UO(2)(CO(3))(3)],(5)(-) confirming the reversibility of this reduction.

Journal Article↗

Budesonide but not nedocromil sodium reduces exhaled nitric oxide levels in asthmatic children.

Exhaled nitric oxide (ENO) has been proposed as a marker of airway inflammation in asthma and could be useful to evaluate the response to anti-inflammatory treatment. We investigated the effect of budesonide and nedocromil sodium on ENO levels and lung function in asthmatic children. Twenty stable steroid-naïve asthmatic children were randomized in a single blind, cross-over study to receive inhaled budesonide (group A) or nedocromil sodium (group B) for 6 weeks. ENO was measured with a chemiluminescence analyser at baseline and at the end of each treatment period. Repeated-measures ANOVA was carried out. In asthmatic baseline ENO levels [mean 32.5 ppb, 95% confidence interval (CI) 26.4 to 38.7] were significantly higher compared to reference values (8.7 ppb, 95% CI 8.1 to 9.2, P<0.001). There were no treatment-order effect, no carry-over effect and in both groups the response pattern was the same: budesonide significantly lowered ENO levels from 41.0 ppb to 22.8 ppb in group A (mean, P<0.01) and from 22.6 ppb to 13.0 ppb in group B, (mean, P<0.05), while nedocromil did not reduce ENO values (from 24.4 ppb to 22.6 ppb in group B and from 22.8 ppb to 38.0 ppb in group A, mean, P = NS and P<0.01 respectively). After budesonide treatment ENO values of asthmatics were still significantly higher than in healthy children The baseline values of FEV1 and FEF(25-75) were normal in both groups and no significant changes were observed during the study. In conclusion, our study shows that budesonide, but not nedocromil sodium, significantly reduces ENO levels in stable asthmatic children even in absence of changes in the lung function.

Adolescent↗

Total serum IgE and outcome in infants with recurrent wheezing.

OBJECTIVE: To investigate the relation between total serum IgE at 0.5-3 and 3-6 years, and the risk of allergic sensitisation and persistent wheezing up to 8 years of age. METHODS: Prospective follow up study of 45 infants with highly recurrent wheezing, no allergic symptoms, and negative skin tests. RESULTS: In the last follow up year, 15 children still suffered from wheezing. Five wheeze-free and four episodically wheezing children had become sensitised. No association was found between early (0.5-3 years) IgE z scores and the recurrence of wheezing during follow up, or atopic sensitisation. IgE z scores at 3-6 years were significantly higher in children with positive skin tests (p = 0.013), but were still not associated with recurrence of wheezing. CONCLUSIONS: In subjects with frequent early wheezing and no signs of atopy, early total serum IgE measurements are not predictive of outcome.

Age Factors↗

Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers.

Three types of tachykinin receptors, NK(1), NK(2)and NK(3), have been described to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mononuclear ones, and points to their involvement in lung pathophysiology. We previously reported that NK(1)and NK(2)receptors are present on monocytes (MO) isolated from healthy donors or rheumatoid patients - a greater sensitivity to NK(2)receptor stimulation was observed in the latter condition. This study evaluated the effects of SP and NKA, as well as NK(1)and NK(2)selective agonists and antagonists, on MO obtained from healthy volunteers, healthy smokers or patients with interstitial lung diseases (e.g. sarcoidosis and idiopathic pulmonary fibrosis). Superoxide anion (O(2)(-)) production was chosen as a parameter of cell activation. SP and NKA dose-dependently evoked O(2)(-)production from MO in all the conditions evaluated, their effects being competitively antagonized by selective antagonists (CP 96 345 and MEN 10 627, respectively). When selective NK(1)and NK(2)agonists were used, [Sar(9)Met(O(2))(11)]SP, a selective NK(1)agonist, induced a more than doubled O(2)production in MO obtained from patients with interstitial lung diseases as compared to healthy volunteers, whereas MO isolated from healthy volunteers were more sensitive to NK(2)receptor stimulation.

Adult↗

Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin. Neither metformin or placebo significantly modified the levels of LH, FSH, dehydroepiandrosterone sulphate, and progesterone in any group, whereas testosterone concentrations decreased only in PCOS women treated with metformin. SHBG concentrations remained unchanged in all PCOS women; whereas in the control group, they significantly increased after both metformin and placebo. Leptin levels decreased only during metformin treatment in both PCOS and control groups. (ABSTRACT TRUNCATED)

Abdomen↗

[Cerebral oxygenation and near-infrared rays spectrophotometry].

Near infrared spectroscopy (NIRS) is a new technique which allows non invasive bedside monitoring of cerebral oxygenation and hemodynamics by measuring relative changes in cerebral oxy- and deoxyhaemoglobin and cytochrome aa3. We have applied this technique to evaluate the possible effects on cerebral oxygenation and hemodynamics of clinical procedures usually performed on preterm infants:--endotracheal suctioning, and we have demonstrated that the magnitude and the duration of the negative effects of open system are significantly reduced using closed endotracheal suctioning system;--withdrawal and infusion through umbilical vein and artery cause significant changes in cerebral hemodynamics: these effects are significantly reduced after administration of ibuprofen;--treatment of patent ductus arteriosus with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability compared to indomethacin and ibuprofen administration also does not affect cerebral vasoreactivity to arterial carbon dioxide tension;--administration of different types and doses of natural surfactant causes different changes in cerebral hemodynamics and these effects seem to be dose-related. Therefore NIRS is an useful device to investigate cerebral oxygenation state of preterm infants and new possibilities could derive from the introduction of a new NIRS method which allows to measure the tissue oxygenation index.

Blood Transfusion↗

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome.

OBJECTIVES: To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. DESIGN: A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. SUBJECTS: Seventeen obese non-diabetic males with a body mass index (BMI) >28 and eight normal-weight controls were examined. MEASUREMENTS: Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waist-to-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 microg) and arginine vasopressin (AVP) (0.3 IU). RESULTS: As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P < 0.05) in obese subjects than in controls, whereas no significant difference in cortisolAUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coefficients between total and incremental ACTH(AUC 0-30 min) and CortisolAUC 0-30 min and all other variables were analyzed. A significant correlation coefficient was present between them and all anthropometric parameters, fasting insulin and insulinAUC, but not with androgens and gonadotrophins. In addition, a significant correlation was present between total and incremental ACTH(AUC 0-30 min) and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coefficients became non-significant, except the one between incremental ACTH(AUC 0-30 min) and insulinAUC (P < 0.05). CONCLUSION: These findings indicate that obese men may also have an altered pituitary response to combined CRH/AVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRH/AVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.

Adipose Tissue↗

Secretion of major adrenal androgens following ACTH administration in obese women with different body fat distribution.

To investigate whether obese female subjects with abdominal obesity may have adrenal androgen hypersecretion, we examined two groups of women with abdominal (n = 12) and peripheral (n = 13) obesity (defined by body mass index and waist-to-hip ratio) and a group of seven healthy normal-weight women. All subjects underwent the following protocol study that included a) baseline determination of major adrenal androgens, b) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microg/Kg BW, e.v.), at 90 min intervals, with blood samples taken for cortisol and androgens, c) an oral glucose tolerance test, performed by administering glucose (75 gr), with blood samples taken for glucose and insulin determination. Each woman also underwent a control saline study. We then investigated the relationships between basal and stimulated androgen levels, body weight and fat distribution and fasting and stimulated insulin levels. Although basal cortisol levels were similar, their increase (as AUC) after the ACTH test was higher in women with abdominal obesity than in the other groups. On the contrary, there were no significant differences in basal and stimulated serum levels of dehydroepiandrosterone, androstenedione and 17-hydroxyprogesterone among the three groups. Fasting and stimulated (as AUC) insulin levels were significantly higher (p < 0.05) in women with abdominal obesity than in those with peripheral obesity and controls. No significant correlation was present between basal and stimulated androgen levels and body mass index, the waist-to-hip ratio or basal and stimulated cortisol values. Therefore, our data indicate that adrenal androgen secretion following low-dose ACTH administration in premenopausal women does not seem to be a function of body fat mass, fat distribution and insulin levels, nor does it correlate with the capacity of the adrenal glands to secrete cortisol in both basal and stimulated conditions.

17-alpha-Hydroxyprogesterone↗

Achievement of near-normal body weight as the prerequisite to normalize sex hormone-binding globulin concentrations in massively obese men.

OBJECTIVE: To investigate the effects of weight loss on sex hormone-binding globulin (SHBG) in massively obese males and whether normal SHBG concentrations could be obtained regardless or not of the achievement of normal body weight values. DESIGN AND SUBJECTS: Sera were collected for SHBG determination from 63 massively obese men, partly before they underwent biliopancreatic diversion (pre-op group = 11) and partly during the post-surgical follow up (post-op group = 52), and twenty normal weight healthy control men. MEASUREMENTS: Serum SHBG was measured using a noncompetitive liquid-phase immunoradiometric assay. RESULTS: Baseline general characteristics were similar in both obese groups. Obese patients in the post-op group had lost 46.4 +/- 2.9 kg since they had undergone operation, namely during a mean period of 14.9 +/- 13.8 (range 1-58) months follow up. Obese groups had significantly lower SHBG than normal weight controls (66.2 +/- 18.6 nmol/l). However, pre-op obese (19.9 +/- 5.5 nmol/l) had significantly lower values than post-op obese subjects (45.5 +/- 24.8 nmol/l; P < 0.001). There were a highly significant correlation between SHBG and individual BMI values (r = -0.629; P < 0.001). Moreover, the post-op obese with BMI values lower or equal to 28 had significantly higher SHBG concentrations than those with BMI greater than 28 (62.8 +/- 22.2 nmol/l vs 32.1 +/- 19.6 nmol/l; P < 0.001), but not significantly different with respect to normal weight controls. CONCLUSIONS: Massively obese men weight loss can completely reverse SHBG abnormalities, which can be restored to the normal range when near-normal body weight is achieved. Since reduced SHBG concentrations can be an independent risk factor for the development of diabetes and cardiovascular disease, this represents an additional benefit of weight loss program in massively obese individuals.

Adult↗

Respiratory rate and body mass in the first three years of life. The working party on respiratory rate.

The correlation between respiratory rate and body mass in the first three years of life was examined in 635 infants and children, aged between 15 days and 3.5 years. Assessments were made during quiet sleep and when awake and calm. Their body weight (2.8-20.5 kg) was measured at the same time. Respiratory rate decreased exponentially with increasing body weight. After log transformation of the data, a linear correlation was found between log(respiratory rate) and log(body weight) both during the sleeping and the wakeful states. For each body weight group, boys had about a 6.5% higher respiratory rate than girls, but both the boys' and the girls' lines were parallel. The slope of the line was -0.43 during sleep and -0.41 during wakefulness, indicating that the respiratory rate: body weight ratio is not a constant in either state, and that it decreases as body weight increases. Adding age to the model did not significantly increase the precision of the fitting. A simple equation of the form respiratory rate = a body weight(b), can accurately describe the decrease in respiratory rate with growth. Smaller (hence younger) infants and children have a higher respiratory rate per unit body weight than larger (hence older) children.

Body Weight↗

Screening for developmental dysplasia of the hip: from theory to practice. Collaborative Group DDH Project.

OBJECTIVE: To evaluate an organizational model for neonatal population screening for developmental dysplasia of the hip. METHODS: In 4648 neonates born in six hospitals of the Lombardy region, screening for developmental dysplasia of the hip was done using the Ortolani-Barlow maneuver and ultrasonography. RESULTS: The frequency of positive results of clinical and ultrasound examinations carried out in the hospitals varied considerably as a result of difficulties in the Ortolani-Barlow test reproducibility and in the low sensitivity of the clinical examination when compared to ultrasonography. Neonatal screening results implied a large number of subjects with a IIa hip, according to Graf's system; as these subjects require follow-up, the cost of this type of screening is high. Ultrasound findings were normal at 69 days of life in 88% and 75% of subjects, respectively, with unilateral and bilateral type IIa hip. CONCLUSION: This study evaluated various organizational models for screening (for different time periods and for selected populations) in relation to the cost-benefit ratio and demonstrated the different problems that still impede identification of a correct screening model.

Hip Dislocation, Congenital↗

Retinopathy of prematurity and antenatal corticosteroids. The Italian ROP Study Group.

OBJECTIVES: It is not known whether antenatal corticosteroids (ANS) can reduce the risk of retinopathy of prematurity (ROP). The aim of this study was to evaluate in a prospective cohort study the effect of ANS on ROP development and severity. METHODS: All infants consecutively admitted to 14 centres from 1.1.1992 to 31.12.1993, with a gestational age < or = 30 weeks, no congenital anomalies, and who survived to 6 months, were enrolled (N = 380). Mean birth weight of the cohort was 1157 g; mean gestational age was 28.4 weeks. ROP stage 1-2 developed in 82 neonates; ROP stage 3-3+ in 57. Only 70 neonates (18.4%) received ANS prophylaxis. RESULTS: ANS prophylaxis highly significantly reduced the risk of developing ROP [Odds ratio, (OR), 0.35; 95% confidence interval 0.17-0.71, logistic regression analysis], and that of severe (stage 3-3+) ROP (OR 0.07; 95% confidence interval: 0.02-0.34). Short gestation, low birth weight, bronchopulmonary dysplasia also were significantly associated with ROP development and severity; respiratory distress syndrome and not being treated with surfactant were significant risk factors for ROP severity. CONCLUSIONS: ANS prophylaxis protected both against ROP development and against severe forms of ROP. Prematurity and respiratory morbidity still represent independent risk factors for ROP.

Adrenal Cortex Hormones↗

Occlusion maneuver to detect the relative contribution of the rib cage and abdomen to tidal volume using respiratory inductive plethysmography in infants.

Respiratory inductive plethysmography (RIP) records movements of the rib cage (RC) and abdomen (AB). A calibration procedure is needed to determine their relative contribution to tidal volume. We evaluated the hypothesis that the relative contribution of the RC and AB could be defined from respiratory efforts made during a brief occlusion of the airways in 10 infants aged 6.5-19 months, who were studied in quiet sleep. Six occlusions were performed during tidal breathing, with and without a pneumotachograph (PNT) and face mask in place. We analyzed the periods of occluded respiratory effort when RC and AB were in opposite directions (paradoxical movements), plotting RC vs. AB and performing a least-squares linear regression to estimate the ratio of the coefficients of AB/RC. Multiple linear regression of AB and RC over tidal volume during about 100 seconds of tidal breathing provided a reference standard. A ratio of 1 means that AB and RC make equal contributions to tidal volume. The feasibility of the occlusion maneuver was poor; only 51% of occlusions with PNT and 54% without led to a paradoxical movement with a good fit (r > 0.9). The mean coefficient of variation (range) was 9.35% (3.9-15.3%) with PNT and 12.1% (2.5%-26.3%) without it. The accuracy was very poor, with the mean AB/RC value being 0.94 with occlusions and 2.39 with multiple linear regression. The mean difference was 1.45 (SD 0.80), yielding 95% confidence limits for the difference of 0.12-3.01. We concluded that, due to its very poor accuracy and feasibility, the occlusion technique is not a useful method to calibrate RIP in infancy.

Abdomen↗

Changes in respiratory rate affect tidal expiratory flow indices in infants with airway obstruction.

Among the tidal expiratory flow measurements that have been suggested as surrogate tests for airway obstruction, a short time to reach peak tidal expiratory flow (t(pef)) is the most widely used. Time to peak expiratory flow is most often expressed as the ratio between t(pef) and total expiratory time (t(e)). As te strictly depends inversely on respiratory rate (RR), we studied the hypothesis that an increase in RR (and a fall in t(e)) with the development of airway obstruction during methacholine or histamine challenge in infants could mask a decrease of t(pef) when expressed as t(pef)/t(e). Thirty-three infants (ages 6.5-23 months) with recurrent wheeze were studied during sedated sleep. Runs of tidal breathing and maximal expiratory flow at FRC (V(maxFRC)) measured by the squeeze technique were obtained before and after the challenge. All infants responded to the challenge: the median fall in P(tCO2) was 25%, and it was 43% in V(maxFRC). RR increased from a median value of 31.1 to a median of 35.1 breaths/min. Both t(pef) and t(e) were significantly shorter after the challenge (P < 0.001 and 0.004, respectively); however, the decrease in t(pef)/t(e) was not significant (P=0.081). The change in t(pef)/t(e) was positively correlated with the change in RR (r = 0.51, P = 0.003). To analyze better the effect of changes in RR on various indices, we divided the patients into two groups: in 17 subjects with a small increase in RR (< 10%), t(e) did not change significantly, while t(pef) and t(pef)/t(e) did; in 16 subjects with a more marked increase in RR (> or = 10%), the shortening of te masked the simultaneous shortening of t(pef), so that t(pef)/t(e) did not change. These data demonstrate that t(pef)/t(e) cannot be reliably used to evaluate changes in airway obstruction when concomitant changes in RR occur.

Airway Obstruction↗