Total Body Plethysmography Research Articles

Small Airway Dysfunction in Children With Controlled Asthma

IntroductionAsthma is characterized by chronic inflammation of the central and distal airways. The aim of this study was to assess the small airway (SA) of children with moderate-severe asthma with normal FEV1. MethodsThis was an open-label, prospective, observational, cross-sectional study with consecutive inclusion of patients with moderate-severe asthma, receiving standard clinical treatment, with normal baseline FEV1. We determined multiflow FEno (CAno), oscillatory resistance and reactance (R5–R20, X5), forced spirometry (FEV1, FEF25–75), total body plethysmography (RV/TLC) and bronchodilation test. SA involvement was defined as: CAno >4.5ppb, R5–R20 >0.147kPa/L/s, X5 <−0.18kPa/L, FEF25–75 <−1.65 z-score, RV/TLC >33%. Poor asthma control was defined as ≤19 points on the ACT questionnaire or ≤20 on the c-ACT. ResultsIn a cohort of 100 cases, 76 had moderate asthma and 24 had severe asthma; 71 children were classified as poorly controlled and 29 were well-controlled. In total, 77.78% of the group with all the correct determinations (n=72) showed ≥ 1 altered SA parameter and 48.61% ≥ 2 parameters. There were no differences between well-controlled or poorly controlled cases. ConclusionsChildren with moderate-severe asthma, with normal FEV1, show a phenotype of dysfunctional SA. In our series, the evaluation of SA using the techniques described above did not provide information on disease control.

Disfunción de la pequeña vía aérea en niños con asma controlada

IntroductionAsthma is characterized by chronic inflammation of the central and distal airways. The aim of this study was to assess the small airway (SA) of children with moderate-severe asthma with normal FEV1. MethodsThis was an open-label, prospective, observational, cross-sectional study with consecutive inclusion of patients with moderate-severe asthma, receiving standard clinical treatment, with normal baseline FEV1. We determined multiflow FEno (CAno), oscillatory resistance and reactance (R5-R20, X5), forced spirometry (FEV1, FEF25-75), total body plethysmography (RV/TLC) and bronchodilation test. SA involvement was defined as: CAno>4.5 ppb, R5-R20>0.147kPa/L/s, X5<−0.18kPa/L, FEF25-75<−1.65 z-score, RV/TLC>33%. Poor asthma control was defined as ≤ 19 points on the ACT questionnaire or ≤ 20 on the c-ACT. ResultsIn a cohort of 100 cases, 76 had moderate asthma and 24 had severe asthma; 71 children were classified as poorly controlled and 29 were well-controlled. In total, 77.78% of the group with all the correct determinations (n=72) showed ≥ 1 altered SA parameter and 48.61% ≥ 2 parameters. There were no differences between well-controlled or poorly controlled cases. ConclusionsChildren with moderate-severe asthma, with normal FEV1, show a phenotype of dysfunctional SA. In our series, the evaluation of SA using the techniques described above did not provide information on disease control.

Blood Shift During Cough: Negligible or Significant?

Rationale: It was reported how forceful rhythmic coughing can provide effective blood flow during ventricular fibrillation without direct chest compression. This mechanism of cough-assisted cardiopulmonary resuscitation constitutes a form of “cardiac massage” secondary to the intrathoracic and intra-abdominal pressure changes during cough. We have previously shown that significant blood shifts (BSs) occurs from the thorax to the extremities during expulsive maneuvers and that abdominal pressure controls the outflow of blood from the splanchnic vasculature. This mechanism was called abdominal circulatory pump. BS was quantified by using double body plethysmography (DBP), which combines total body plethysmography and opto-electronic plethysmography.Aim: We hypothesized that coughing activates also the abdominal circulatory pump, being an additional mechanism that displaces a circulatory output sufficient to maintain consciousness in a patient with a non-beating heart.Methods and Results: We studied seven healthy subjects (age: 28.6 ± 2.5 years) during series of voluntary coughs at three different operating volumes: after a spontaneous tidal volume, at total lung capacity (TLC) and at an intermediate volume. BS from the thorax to the extremities were measured by DBP during quiet breathing and during cough at each operating lung volume. BS during cough resulted significantly higher than during quiet breathing (p < 0.05). During the compressive phase, the blood outflow is around 200 ml, whereas during the expulsive phase BS increased (p < 0.05) with increasing operating volume, being almost 700 ml at TLC. At lower operating volume it is almost 400 ml.Conclusion: Deep, vigorous coughing and the consequent fluctuations in intra-thoracic and intra-abdominal pressure activate both the thoracic and the abdominal pump mechanism. The former leads the low-resistance pulmonary veins to empty into the left heart. The latter can generate a circulatory output from the splanchnic region, which acts as a blood reservoir, to other body tissues. These findings might help to better understand the cardiopulmonary interactions during cough, particularly in patients with unstable cardiac function, and the mechanism by which coughing during unstable cardiac rhythms can maintain consciousness in human subjects.

Pulmonary function in former very low birth weight preterm infants in the first year of life.

Pulmonary function in former preterm infants may be compromised during childhood. To assess pulmonary function in very-low-birth-weight preterm infants at 6-12 months of corrected age and analyze the factors associated with abnormal pulmonary function. Cross-sectional study with preterm infants at 6-12 months of corrected age with birth weight <1500 g. Children with malformations or affected by neuromuscular and respiratory diseases were excluded. Forced expiratory flows were assessed using the chest compression technique, and volumes were measured by total body plethysmography. Pulmonary function parameters in preterm infants were compared to a control group of same-aged children born at term. We studied 51 preterm and 37 infants born at term. Preterm infants had: gestational age at birth (30.0 ± 2.5 weeks), birth weight (1179 ± 247 g), 27.5% had bronchopulmonary dysplasia, and 45% received mechanical ventilation. Preterm infants had lower median z-scores in comparison to term infants for the following parameters (p < 0.05): FVC (-0.3 vs. 0.7), FEV0.5 (-0.5 vs. 0.9), FEV0.5/FVC (-0.6 vs. -0.5), FEF50 (-0.4 vs. 0.9), FEF75 (-0.3 vs. 0.8), FEF85 (-0.1 vs. 0.6) and FEF25-75 (-0.5 vs. 1.1). No term child had abnormal lung function, compared to 39.2% of preterm infants (p = 0.001). Factors associated with abnormal pulmonary function were lower gestational age at birth, small for gestational age, need for mechanical ventilation and presence of recurrent wheezing. Preterms had a high prevalence of abnormal pulmonary function and lower pulmonary function in comparison to term infants. Prematurity, intrauterine growth restriction, respiratory support and recurrent wheezing were associated with abnormal pulmonary function.

1315 Lung Function in Hyperoxia Experimental Model of Newborn Rats

Background and aims: Study of lung function in anexperimental model of bronchopulmonary dysplasia(BPD) induced by hyperoxia in newborn rats. Methods: The subjects of this study were twolitters of Sprague-Dawley rats. Group C (Control):exposure to room air. Group H (Hyperoxia): exposureto 60% of Oxygen from birth and during 14 days. The lung function tests were performed on day 15. Respiratory functional evaluation through a systemof total body plethysmography (Buxco Electronics, Troy, NY, USA): non-invasive analysis system, withthe animal conscious and free, housed in a sealedcontainer. Changes of pressure and volume in thecabin due to respiratory movements are monitoredand used to calculate ventilatory parameters usinga computer application. Results: Two litters with 14 offspring each werestudied. Pulmonary function tests showed adecrease in tidal volume (H: 0.098 ml, C: 0.125 ml, p0,000) with offsetting increase in respiratory rate (H:310 rpm; C: 266 rpm; p 0,03) without differences inminute volume (H: 29.92 ml / min, C: 32.75 ml / min;p 0,186). The index of airway obstruction (Penh) isaltered in the litter exposed to oxygen (p 0, 026). Conclusions:

Optimizing Performance of Respiratory Airflow Resistance Measurements

In contrast to spirometry, airflow resistance determinations provide an effort independent measure of the airway status and allow measurement in individuals unable or unwilling to provide adequate effort during spirometry. Resistance measurements may be performed using an esophageal balloon, airflow perturbation techniques (including interrupter and oscillatory techniques), or total-body plethysmography. Esophageal balloons are invasive, and airflow perturbation techniques are becoming more widely used. Airflow perturbation methods assess small airway dysfunction using frequency dependence of resistance, a surrogate for frequency dependence of compliance. Body plethysmography remains the "gold standard" for measuring airway resistance and is based on measures of pressure changes and flows with the patient enclosed in a body plethysmograph. While plethysmographic procedures may be completed rapidly, yielding multiple trials within preset repeatability criteria, the equipment is costly and the operator must be highly trained. Plethysmographic specific resistance loops have definite shapes (morphologies) indicative of specific airway disorders, which may be interpreted in a manner analogous to spirometry. Specific resistance and conductance assess the important effects of lung volumes. Reimbursement for resistance measurements varies depending on regional guidelines.

Computable Linearizations of Well-partial-orderings

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown aetiology which mainly affects women of reproductive age. A growing body of evidence suggests a relation between the disease and estrogenic hormones. In particular, pregnancy and use of estrogens favour the progression of the disease, which is in turn slowed down by menopause. These observations suggested already in the past a treatment strategy based on hormonal manipulation: discontinuation of estrogens containing medications, avoiding pregnancy, inhibition of estrogens activity and induction of menopause. In the present study, conducted on a relatively large population for a rare disease, we sought to show the hormonal manipulation's positive effects for the survival rate. 36 women suffering from LAM were evaluated between January 1985 and March 2005. All our patients were treated with hormonal therapy, following different schemes. The response to the treatment was evaluated in all patients with arterial blood sampling, lung function tests (total body plethysmography, DLCO), measurement of the hormones in the blood, chest and abdomen CT scan. The survival rate since the clinical onset was 97% at the 5 year timepoint, 90% at 10 years, and 71% at 25 years. Previous studies, conducted before the introduction of the hormonal treatment showed a survival rate of 20% at 10 years. Our results highlight the role of the hormonal manipulation as a mainstay in the treatment of LAM, with the capability of reducing mortality and improving the quality of life as well.

Plethysmograph and interrupter resistance measurements in prematurely born young children

Background: Airways obstruction in premature infants is often assessed by plethysmography, which requires sedation. The interrupter (Rint) technique does not require sedation, but has rarely been examined in children under...

Induction of Irradiation Induced Pneumonitis Relies on the CD95/ CD95-L System

Purpose/Objective: Pneumonitis is a dose limiting side effect induced by radiotherapy for any thorax associated neoplasms. For example, pneumonitis can cause symptoms of respiratory failure and results in a lethality rate up to 10 %. Currently, the underlying mechanisms for irradiation induced pneumonitis are not known in detail. Although pneumonitis mostly occurs within irradiated areas of the lung, it may spread to non irradiated areas, indicating that humoral factors may be involved. In parallel to its role in apoptosis induction, the CD95/CD95-L system mediates proinflammatory cytokine responses and attracts neutrophils. It is currently hypothetical that complex alterations of cytokine expression patterns in combination with infectious triggers are of major importance for the induction of pneumonitis. In this regard it has been shown that bacterial infection results in increased CD95/CD95 ligand surface expression and induction of apoptosis and secondly leads to secretion of defensins and cytokines. Furthermore, bleomycin-mediated pneumonitis was significantly diminuated after administration of CD95 antigen or anti CD95 ligand antibody. Since the expression of CD95 and CD95-Ligand (CD95-L) is known to be induced by ionizing irradiation, we investigated if the CD95 system is involved in the pathology of irradiation induced pneumonitis. For this reason, genetic defined mice with a deficiency of the CD95 receptor (lpr), deficiency of the ligand (gld) and control mice with an intact CD95 system (C57BL6/J) were examined on the development of pneumonitis after irradiation. Materials/Methods: Female C57Bl/6J, lpr and gld mice were acclimated to a total-body plethysmograph for a minimum of 2 weeks and enrolled to the research protocol with a body weight of 20g. To evaluate the dysfunction of the lung in pneumonitis, after single irradiation of the right hemithorax with doses of 0/12,5Gy, the breathing frequency was determined twice weekly for the following 30 weeks. Histopathological alterations judged by alveolar wall thickness, interstitial edema, interstitial and peribronchial inflammation were analyzed at days 1, 21, 42, 84 and d210 by using the hematoxyllin-eosine staining. For each of the morphologic alterations noted above, a numerical score was determined. Criteria for scoring for each lesion were assessed as follows: 0 < 10% of the fields viewed; 1= 10–30%; 2= 30–50%; 3= 50–70%; 4≥70% and the cumulative inflammation score was determined. Results: Whereas a highly significant increase of breathing frequency occurred in control mice between days 5–70, no such increase was detectable in gld and lpr mice. Furthermore, no inflammatory response with increasing alveolar wall thickness, interstitial edema, increasing number of inflammatory cells in the interstitial and peribronchial space was neither detected in lpr and gld mice. In contrast, in control mice, a clear inflammatory response was visible (right lung > left lung) with a peak between day 21–42. Conclusions: These results suggest that the CD95/CD95 (Fas-Fas ligand) pathway plays an essential role in the development of pneumonitis. The identification of the CD95/CD95-L-system may offer new options for preventing or treating radiation induced pneumonitis.

Cardiorespiratory and metabolic reactions during entrance into torpor in dormice, Glis glis

Dormice voluntarily enter torpor at ambient temperatures ranging between 0-28 degrees C. This study describes heart rate, ventilation frequency, O2-consumption (defined as metabolic rate), CO2-production and body temperature during entrance into torpor. Their temporal relationship was analysed during the time course of metabolic depression at different ambient temperatures. Body temperature and heart rate were measured in unrestrained dormice with implanted transmitter. Ventilation frequency was monitored by total body plethysmography or infrared video monitoring. To compare entries into torpor at different T(a) these periods were distinguished into four different phases: the resting phase prior to torpor, the phase of pre-torpor adjustments, the reduction phase and the phase of steady state torpor. In the pre-torpor phase, dormice increased their ventilation, metabolic rate and heart rate, indicating that the torpid state is initiated by an enhanced metabolic activity for about an hour. This was followed by a rapid reduction of ventilation, metabolism and heart rate, which reached their minimum values long before body temperature completed its decline. The results of the present study show that the entrance into torpor is caused by an active respiratory, cardiac and metabolic depression.

The effect of ribavirin to treat previously healthy infants admitted with acute bronchiolitis on acute and chronic respiratory morbidity

The role of ribavirin in the treatment of acute bronchiolitis is controversial. It has been suggested that the use of ribavirin may be of benefit during the acute illness and may reduce subsequent recurrent respiratory morbidity. This randomized, double-blind, placebo-controlled study was designed to determine whether ribavirin administered during the acute illness would have an influence on respiratory morbidity during both the acute illness and during the following year. Bronchial reactivity 6 months after the acute illness was also assessed. Forty previously well infants with moderately severe acute bronchiolitis were recruited during three winter epidemics. Subjects received study medication for 18 h a day. Management was otherwise unaltered. Subjects were evaluated daily by the investigator and subsequently assessed at 6 weeks, 6 months and 1 year following the acute illness. Assessment of bronchial hyper-responsiveness was assessed at 6 months of age using total body plethysmography and an established ultra-sonically nebulized distilled water challenge.A total of 40 patients (21 ribavirin, 19 placebo) were entered into the study. The two groups did not differ with respect to age, gender or clinical severity on entry to the trial. No significant differences were identified in the rate of clinical improvement over the first 24 h, the time to discharge, bronchial responsiveness at 6 months of age, frequency of significant respiratory symptoms over the first year of life and the frequency of prescribed bronchodilators and inhaled steroids during the year of follow-up.This study was unable to demonstrate any clinical benefit from the use of ribavirin in the acute illness or during subsequent follow-up for 1 year.

The signal in total-body plethysmography: errors due to adiabatic-isothermic difference

Total-body plethysmography is a technique often employed in comparative physiology studies because it avoids excessive handling of the animals. The pressure signal obtained is generated by an increase in internal energy of the gas phase of the system. Currently, this increase in internal energy is ascribed to heating (and water vapour saturation) of the inspired gas. The standard equation for computing tidal-volume implies that only temperature and saturation differences can be responsible for generating the ventilation signal. In this study, we were able to demonstrate that the difference between the external process of the thoracic expansion, which is adiabatic, and the internal process of it, which is isothermic, is an important factor of internal energy change in the total-body plethysmography method. In other words, organic tissues transfer heat to the entering gas but also to the present gas, in a way that keeps internal expansion an isothermic process. This extra amount of energy was never taken into account before. Therefore, experiments using such a technique to measure tidal-volume should be done using isothermic chambers. Moreover, due to uncertainties of the complementary measurements (ambient and lung temperatures, ambient water vapour saturation) needed to compute tidal-volume using total-body plethysmography, a minimal temperature difference about 15°C between body and ambient should exist to keep uncertainties in tidal-volume values below 5%. However, this limit is not absolute, because it varies as a function of humidity and degree of uncertainty of the complementary measurements.

Lung volumes before and after lung volume reduction surgery: quantitative CT analysis.

The volume and severity of pulmonary emphysema in individual lungs were measured by means of quantitative computed tomography (CT) studies in 28 patients (14 women, 14 men, median age 65 yr) who underwent either bilateral (n = 15) or unilateral (n = 13) lung volume reduction surgery (LVRS). Spirometric, total body plethysmographic, and CT data (at TLC and RV) were correlated before and after LVRS. Lung volumes determined by CT correlated well with volumes obtained by total body plethysmography (p < 0.0001). For individual lungs after LVRS, CT-derived mean lung capacity decreased 13% and residual volume 20% (p < 0.00001 for each), while mean total functional lung volume (TFLV, defined as the volume of lung with CT attenuation greater than -910 Hounsfield units) increased 9% (p < 0.01), and the mean ratio of the air space to tissue space volume (V(AS)/V(TS)) decreased more at RV (23%) than at TLC (14%) (p < 0.0005 for each). In contrast, unilateral LVRS did not affect exhalation from the unoperated lung (2% reduction in RV, p = NS). The magnitude of the postoperative response (CT-derived TLC, RV, TFLV, V(AS)/V(TS)) of each operated lung was comparable for unilateral and bilateral LVRS. Thus, a lung's response to LVRS was independent from that of the contralateral lung. Moreover, postoperative alterations in TFLV and FEV1 correlated significantly (r = 0.80, p < 0.0001), which suggests that the expansion of functioning tissue may contribute to the mechanism by which LVRS palliates airway obstruction.

Variable response to bronchodilator therapy in young children born prematurely

The response to nebulized therapy was studied at a median postnatal age of 16 months (range 6–24 months) in 15 children born prematurely. Thoracic gas volume (TGV) and airways resistance ( R aw) were measured by total body plethysmography and specific conductance ( SG aw) calculated. The measurements were made prior to, and then 5 and 10 min after, nebulized saline (3 ml), and then 5, 10 and 15 min after administration of nebulized salbutamol (2·5 mg in 2·5 ml normal saline). There was no significant change in TGV throughout the study period. One child showed a significant improvement in airways resistance following nebulized saline, and no child had a significant deterioration. R aw and SG aw both significantly improved in the group overall at 15 min following salbutamol ( P < 0·05, P < 0·03 respectively). Individual patients, however, showed a variable serial response in R aw and SG aw: four children had a paradoxical response (an increase in R aw and a decrease in SG aw) at 5 min and at 10 or 15 min, seven children had a significant improvement (decrease) in R aw and eight a significant improvement (decrease) in SG aw. The children who had an initial paradoxical effect did not differ significantly in either age or baseline lung function from the other infants. Patients in whom R aw and SG aw improved following bronchodilator did not differ in age from the rest of the study group, but had tended to have worse lung function prior to bronchodilator administration. We conclude that there is a variable response to nebulized salbutamol in children born preterm, this treatment should only be administered in association with careful monitoring.

Nebulised water as a bronchoconstricting challenge in infancy.

The pulmonary response to inhalation challenge with nebulised distilled water was measured in 100 sedated infants with a history of wheeze. Lung function was measured by total body plethysmography. Satisfactory results were obtained in 88 infants. Fifty one were considered to have responded by developing a greater than 20% decrease in specific conductance (sGaw) after nebulised water. Thirty two of these infants had previously been challenged with nebulised saline before but only one showed a greater than 20% decrease in sGaw after saline. Twenty infants who developed signs of bronchoconstriction after challenge with nebulised water were rechallenged 20 minutes later. After the initial challenge a fall in sGaw of greater than 20% was found in 19 of the 20. After a second challenge with nebulised water only 15 (75%) showed a 20% or greater decrease in sGaw. Nine of the 20 infants remained sedated and were rechallenged for a third time. Eight showed a greater than 20% decrease in sGaw. This study indicates that approximately 60% of infants with a history of wheeze will bronchoconstrict in response to inhaled nebulised water and that up to 75% show no evidence of a subsequent refractory period to inhaled water challenge.

The effect of peritoneal dialysate on pulmonary function and blood gasses in C.A.P.D. patients

There have been many reports showing diminished vital capacity (VC), total lung capacity (TLC), and functional residual capacity (FRC), after the infusion of peritoneal dialysate in patients on continuous ambulatory peritoneal dialysis (C.A.P.D.) for chronic renal failure. We also examined the effects of the infusion of two litres of dialysate on airways resistance (Raw) using total body plethysmography and on arterial blood gasses. Ten patients on C.A.P.D. were selected. The mean results of dialysate infused (in) and dialysate drained (out) are as follows: FVC 3.66 l (in) and 3.73 l (out) (not significant); VC 3.81 l (in) and 3.99 l (out) (p less than 0.05); FEV1 3.02 l (in) and 2.94 (out) (n.s.); TLC 5.89 l (in) and 6.33 l (out) (p less than 0.05); FRC 3.56 l (in) and 3.78 l (out) (p less than 0.05); Raw 4.79 cmsH21/l/s (in) and 4.72 cmsH20/l/s (out) (n.s.); Pa02 11.03 kPA (in) and 11.35 kPA (out) (p less than 0.001). We conclude that two litre dialysate causes significant reduction of TLC, VC and FRC, and a reduction in Pa02 and A-a02 but has no effect on airways resistance.

Nebulised sodium cromoglycate in infancy: airway protection after deterioration.

Over a two year period 100 infants with histories of wheeze were challenged with nebulised water. They were sedated and lung function measured by total body plethysmography. Thirteen of the 53 infants who developed bronchoconstriction after challenge with nebulised water were given nebulised sodium cromoglycate and rechallenged with nebulised water. All infants were initially challenged with normal saline, after which there was no significant change in lung function. After challenge with nebulised water and sodium cromoglycate there were significant decreases in specific conductance compared with those found after challenge with normal saline. After rechallenge with nebulised water there was no deterioration in lung function. Although sodium cromoglycate caused a deterioration in lung function in these infants, it protected their airways from challenge with nebulised water.

Estimation of lung volume in infants by echo planar imaging and total body plethysmography.

Echo planar imaging (an extremely fast method of magnetic resonance imaging) was used to measure lung volume in a group of nine infants, all of whom had had respiratory problems. The mean echo planar imaging estimate of total lung volume was 44 +/- 9 ml/kg. In each case the right lung was larger than the left (ratio 52.8:47.2%). The mean thoracic gas volume was 36 +/- 8 ml/kg. The entire sequence of images of the thorax (about 400) takes five minutes to complete, infants require no sedation, and there are no side effects.

Nebulised salbutamol does have a protective effect on airways in children under 1 year old.

Ten infants under the age of 1 year each of whom gave a history of recurrent wheezing attacks were studied with a total body plethysmograph. All the infants were free of wheeze when studied and were sedated with chloral hydrate. All 10 showed a significant deterioration in lung function when given nebulised water for two minutes with an increase in airways resistance and a decrease in specific conductance at one and five minutes after nebulisation compared with baseline readings. Measurements returned to baseline values within 15 minutes. When the same amount of nebulised water was given 20 minutes after nebulised salbutamol, however, there was no significant deterioration in lung function at one and five minutes after administration of nebulised water. We conclude that the airways were protected against the bronchoconstricting effect of nebulised water by the beta 2 adrenoreceptor stimulant salbutamol.

Ventilatory changes in the golden hamster, Mesocricetus auratus, compared with the laboratory rat, Rattus norvegicus, during hypercapnia and/or hypoxia

1. 1. Tidal volume, respiratory frequency, and minute volume were measured with total body plethysmography. 2. 2. Both hypercapnic (0–7% CO 2) and hypoxic (13–21% O 2) gas mixtures caused “dose” related hyperventilation in the hamsters. However, there was no synergism between combined stimuli. 3. 3. Rats exhibited greater hyperventilation than the hamsters during hypercapnic + hypoxic and hypercapnic exposures. Hamsters responded more than the rats to hypoxia alone. 4. 4. Greater blood buffering capacity of hamsters is a possible explanation for the species differences in ventilatory sensitivity.