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[Ventilatory response to lung inflation after induced bronchospasm in healthy conscious subjects (author's transl)].

In 10 healthy conscious subjects we have studied the effect of a sustained bronchospasm induced by aerosol of carbachol on the pattern of breathing and the ventilatory response to lung inflation which reflects the Breuer Hering reflex. Bronchospasm was assessed by measuring airway resistance and functional residual capacity by plethysmography. After bronchospasm the ventilatory response to inflation was unchanged and the role played by afferents related to such a reflex in controlling pattern of breathing was preserved. Moreover the ration between the threshold volume of the reflex and tidal volume (VT) remained constant. These data suggest that this ration could represent a central set point for VT control. Variable changes in the ventilatory pattern were also observed and are discussed in relation to the previous data.

Adult↗

Pathophysiology of the respiratory system related to anesthesia.

The pathophysiology of the respiratory system can be viewed by simply evaluating the status of a functional residual capacity (FRC). More specifically, patients with airways that are characterized as extremely compliant or "floppy" will have an increased FRC, which is the hallmark of chronic obstructive pulmonary disease. Patients with noncompliant, "stiff" lungs suffer from a form of restrictive disease with a resultant reduction in the FRC. Hence, the implications for anesthesia care focus on the FRC; that is, raising the FRC in the restrictive disease patient and normalizing or preventing further increase in the FRC in the patient with chronic obstructive pulmonary disease.

Anesthesia↗

Infants with cystic fibrosis: pulmonary function at diagnosis.

Meconium ileus (MEC), failure to thrive (FTT), and a combination of FTT and pulmonary symptoms (COMB) are the most frequent symptoms of cystic fibrosis (CF) at the time of diagnosis. The purpose of this study was to compare to normal controls (NC) the pulmonary function of CF infants at the time of diagnosis, when grouped by these symptoms. The measurements of pulmonary function included oxygen saturation (SaO2), functional residual capacity (FRC), mixing index (MI), total respiratory system compliance (Crs), and maximal flow at FRC (VmaxFRC). Compared to NC (n = 33), the MEC group (n = 5) had a higher MI (54 vs. 42%) and no difference in SaO2, Crs or VmaxFRC. There were no significant differences between FTT (n = 8) and NC groups although there was a tendency for Crs to be lower in the FTT group (5.1 vs. 6.8 ml/cm H2O). When compared to all other groups, the COMB group (n = 11) had significantly lower SaO2, MI, Crs, and VmaxFRC. The normal lung function in the MEC group is consistent with the normal anatomy reported in CF infants dying secondary to meconium ileus. Longitudinal evaluation of the infants in this study, following initiation of care as patients with a diagnosis of CF, may allow us to determine whether symptoms at diagnosis remain an important determinant of lung function in infancy.

Cystic Fibrosis↗

Lung function in 6-20 month old infants born very preterm but without respiratory troubles.

Lung function results of 21 healthy infants born very prematurely are reported. The median gestational age was 29 weeks, but none had developed respiratory distress or required any form of respiratory support in the neonatal period. Lung function was assessed by measurements of thoracic gas volume (TGV) and airway resistance (Raw) plethysmographically, and of functional residual capacity (FRC) using a helium gas dilution technique. Two separate measurements were made between 6 and 20 months of age; all infants were measured once in the first and once in the second year of life. Regression equations were calculated for TGV, Raw, and FRC related to weight, height, and postnatal age. These data provide a new set of values for very preterm infants, in part small for gestational age, without neonatal respiratory trouble.

Age Factors↗

Action of costal and crural parts of the diaphragm on the rib cage in dog.

We studied the action of the costal and crural (vertebral) parts of the diaphragm on the lower rib cage in normal supine dogs. The two parts of the diaphragm were separately stimulated by electrodes directly implanted in the muscle or via the different phrenic nerve roots in the neck. The results of the experiments indicate the following. 1) The costal and crural parts of the diaphragm have a different segmental innervation and a different mechanical action on the rib cage. 2) The costal diaphragm expands the lower rib cage when it contracts. This rib-cage expansion is due mostly to the fulcrum of the abdominal contents and partly to the rise in abdominal pressure that takes place during diaphragmatic contraction. The pericardial attachments play no role in this action of the diaphragm. 3) The action of the crural diaphragm on the lower rib cage depends only on the balance between the inspiratory force exerted by the rise in abdominal pressure and the expiratory force exerted by the fall in pleural pressure. In the intact animal at functional residual capacity, these two opposite effects cancel each other. 4) The inflationary action of both parts on the rib cage decreases progressively as lung volume increases. The findings also suggest that the rise in abdominal pressure which occurs when the diaphragm contracts expands the lower rib cage by acting through the area of apposition of the diaphragm to the rib cage. These findings also strengthen the idea that the diaphragm actually consists of two muscles.

Abdomen↗

Hyperinflation in children with liver disease due to alpha-1-antitrypsin deficiency.

Fifty-nine patients (median age 6.0 years) with liver disease and ten healthy children without liver disease (median age 7.5 years) had serial measurements of functional residual capacity (FRC) over a period of at least 6 months. Twenty-eight children with alpha-1-antitrypsin deficiency (A1ATD) tended to have higher lung volumes than 26 with extrahepatic biliary atresia (EHBA). Fifteen children had persistent hyperinflation (FRC greater than 120% predicted for height; 2 SD above the mean of controls); in five children (four with A1ATD) this was unresponsive to bronchodilator therapy. Two of the children with A1ATD who had persistent unresponsive hyperinflation on three serial measurements were only 3 and 4 years of age. No healthy child without liver disease was hyperinflated. These results suggest that A1ATD may be associated with lung function abnormalities even in very young children.

Biliary Atresia↗

Randomised trial of inhaled steroids in preterm infants with respiratory symptoms at follow up.

BACKGROUND: Preterm infants often suffer from recurrent respiratory symptoms at follow up. Although these infants are responsive to treatment with bronchodilators some continue to wheeze or cough despite treatment. In a randomised double blind placebo controlled trial, the ability of inhaled steroids to reduce recurrent respiratory symptoms and the requirement for bronchodilator treatment in preterm infants less than two years of age has been assessed. METHODS: Eighteen premature infants with mean gestational age 28 weeks and postnatal age 10.5 months were recruited. The study consisted of two six week treatment periods separated by a two week washout period. The infants received either 200 micrograms of beclomethasone dipropionate or placebo as one puff twice daily from an inhaler, through a spacer and a face mask. Parents kept a daily record of their infants' respiratory tract symptoms (wheeze and cough) and use of bronchodilators. Functional residual capacity (FRC) was measured at the beginning and end of each six week period. RESULTS: The symptom score was reduced by 37% in the active compared with the placebo period. During the active period the infants had a mean of 28 bronchodilator free days, compared with 22 days in the placebo period. The FRC improved significantly in the active but not the placebo period. CONCLUSION: Regular dosage with beclomethasone by inhalation is a useful treatment for preterm infants with respiratory symptoms.

Administration, Inhalation↗

Effects of CPAP on lung mechanics in infants with acquired tracheobronchomalacia.

Continuous positive airway pressure (CPAP) has been used in the treatment of infants with tracheobronchomalacia (TBM). However, the effects of CPAP on lung mechanics in these infants are unknown. We hypothesized that CPAP prevents airway collapse and improves forced exhalation. We studied respiratory mechanics of nine infants (age 15 +/- 3 mo, SEM) with acquired TBM documented by bronchoscopy, during quiet respiration and forced exhalation, using the esophageal balloon and rapid thoracic compression techniques, respectively. Measurements were made when infants received no CPAP and repeated when 5 and 8 cm H2O CPAP were applied to the airway opening via a modified Mapleson anesthesia circuit. Expiratory resistance (RL), midexpiratory tidal flow (VE50), and maximal flow at functional residual capacity (Vmax FRC) were compared at each level of CPAP. Vmax FRC increased threefold from baseline to 8 cm H2O CPAP (p < 0.005). In contrast, there was no difference in expiratory RL or in VE50 at any level of CPAP. These data suggest that in infants with acquired TBM, assessments of forced expiratory flow reflect the amount of CPAP necessary to prevent airway collapse during forced exhalation better than can measurements of tidal mechanics.

Airway Resistance↗

Lung function, airway responsiveness, and respiratory symptoms before and after bronchiolitis.

Acute viral respiratory illness during infancy has been implicated as a precursor for subsequent lower respiratory morbidity in childhood. A prospective, longitudinal study of respiratory function, airway responsiveness, and lower respiratory illness during early childhood was performed in a cohort of 253 healthy infants to characterise those who experienced bronchiolitis. Seventeen infants (7% of the cohort), were given a diagnosis of bronchiolitis during the first two years of life with two (1%) requiring hospital admission. Seventy one per cent of those infants with bronchiolitis had a family history of atopy, 53% of asthma, and 29% had a mother who smoked cigarettes. These family history characteristics in this group with bronchiolitis were not different from the rest of the cohort. There were also no differences in the number of older siblings, the number breast fed, the duration of breast feeding, or socioeconomic status of the families between those that did and did not get bronchiolitis. Respiratory function was assessed at 1, 6, and 12 months of age. Maximum flow at functional residual capacity (VmaxFRC) was measured using the rapid thoracic compression technique. Resistance (Rrs) and size corrected compliance (Crs/kg) were obtained from a single brief occlusion at end inspiration. Airway responsiveness was assessed by histamine inhalation challenge and the provocation concentration of histamine resulting in a 40% fall on VmaxFRC from baseline (PC40) was determined. Respiratory measurements were ranked into terciles to assess the distribution of infants who developed bronchiolitis through the cohort. Cough and wheeze were noted to be frequent before the episode of bronchiolitis. This study has demonstrated that infants who develop bronchiolitis have evidence of pre-existing reduced respiratory function and lower respiratory symptoms. It is proposed that bronchiolitis, although potentially contributory, is not usually causative of subsequent lower respiratory morbidity.

Asthma↗

Impact of different inspiratory flow patterns on arterial C02-tension.

Ventilation with decelerating inspiratory flow is known to reduce the dead space fraction and to decrease PaCO2. Constant inspiratory flow with an end-inspiratory pause (EIP) is also known to increase the removal of CO2. The aim of the study was to elucidate the effect of the pause/no-flow period while both the pattern and rate of inspiratory flow was unchanged, and when the lung was ventilated with sufficient PEEP to prevent end-expiratory collapse. Surfactant depleted piglets were assigned to decelerating or constant inspiratory flow with 24 breaths per minute (bpm) or 12 bpm, or to constant flow, without and with an end-inspiratory pause of 25%. By adding an EIP the total time without active inspiratory flow of the respiratory cycle was kept unchanged. Gas exchange, airway pressures, functional residual capacity (using sulfurhexafluoride) and haemodynamics (thermo-dye indicator dilution technique) were measured. Irrespective of ventilatory frequency, PaCO2 was lower and serial dead space reduced with decelerating flow, compared with constant inspiratory flow. With an end-inspiratory pause added to constant inspiratory flow, serial dead space was reduced but did not decrease PaCO2. The results of this study corroborate the assumption that total time without active inspiratory flow is important for arterial CO2-tension.

Animals↗

Effects of reduced frequency breathing on arterial hypoxemia during exercise.

It is uncertain that exercise with reduced frequency breathing (RFB) results in arterial hypoxemia. This study was designed to investigate whether RFB during exercise creates a true hypoxic condition in arterial blood by examining arterial oxygen saturation (SaO2) directly. Six subjects performed ten 30 s periods of exercise on a Monark bicycle ergometer at a work rate of 210 W alternating with 30 s rest intervals. The breath was controlled to use 1 s each for inspiration and expiration, and two trials with different breathing patterns were used; a continuous breathing (CB) trial and an RFB trial consisting of four seconds of breath-holding at functional residual capacity (FRC). Alveolar oxygen pressure during exercise showed a slight but significant (p less than 0.05) reduction with RFB as compared to CB. However, a marked increase in alveolar-arterial pressure difference for oxygen (A-aDO2) (p less than 0.05) with RFB over CB resulted in a marked (p less than 0.05) reduction in arterial oxygen pressure. Consequently, SaO2 fell as low as 88.8% on average. Additional examination of RFB with breath-holding at total lung capacity showed no increases in A-aDO2 in spite of the same amount of hypoventilation as compared with that at FRC. These results indicate that RFB during exercise can result in arterial hypoxemia if RFB is performed with breath-holding at FRC, this mechanism being closely related to the mechanical responses due to lung volume restriction.

Adult↗

Effects of non-REM sleep on ventilation and respiratory mechanics in adults with cystic fibrosis.

To determine the effects of sleep upon respiratory function, five adult patients with cystic fibrosis (CF) were monitored during sleep in a horizontal body plethysmograph. Tidal volume (VT) decreased during non-rapid-eye-movement (NREM) sleep, resulting in a NREM sleep-associated decrement in minute ventilation (VI = 11.10 +/- 0.67, 9.32 +/- 0.91, and 9.17 +/- 1.42 L during wakefulness, stage 2, and stages 3-4, respectively, p < 0.05). There were no NREM sleep-associated changes in respiratory frequency (f) or inspiratory time (Ti), but respiratory neuromuscular output was reduced during NREM sleep P0.1 = 3.33 +/- 0.57, 1.79 +/- 0.23, and 1.99 +/- 0.21 cm H2O during wakefulness, stage 2, and stages 3-4, respectively, p = 0.005). Upper airway resistance (Rua), lower airway resistance (RIa), and lung volume did not change in association with NREM sleep. Functional residual capacity (FRC) measurements made using helium dilution indicated large volumes of trapped gas, likely a result of peripheral airways that were closed at FRC. We conclude that in adult patients with CF, NREM sleep is associated with a decrement in VT and VI, NREM sleep does not alter airflow resistance or lung volume, and the observed reductions in VT and VI apparently result from a NREM sleep-associated decrease in respiratory neuromuscular output.

Adult↗

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease.

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.

Birth Weight↗

Do lung volumes change with sleep state in the neonate?

We have studied 12 healthy full-term babies, mean age 3.2 days, using physiological criteria--EEG, electrooculogram, electromyogram, respiratory regularity and visible movement--to assess sleep state, and a respiratory jacket to record changes in functional residual capacity (FRC). A total of 593 min of sleep data were analysed. Of the recordings, 39% were scored as quiet sleep, 40% as active and 21% as indeterminate sleep. The mean maximum variation in FRC overall was 29 ml (SD +/- 15.4 ml). Examination of these figures showed that FRC variations during sleep state changes were smaller than those seen within a defined sleep state. We conclude that changes in sleep state are not associated with variations in FRC.

Functional Residual Capacity↗

Lung volumes, mechanics, and oxygenation during spontaneous positive-pressure ventilation: the advantage of CPAP over EPAP.

To determine if continuous positive airway pressure (CPAP) or expiratory positive airway pressure (EPAP) is superior for achieving or maintaining effective lung volume in spontaneously breathing critically ill patients in acute respiratory failure, the authors measured functional residual capacity (FRC), airway and esophageal pressures, and arterial oxygen tensions when CPAP and EPAP were 5 and 10 cm H2O. Arterial oxygenation, FRC, and transpulmonary pressure at end-expiration were greatest when CPAP was 10 cm H2O. Lung compliance did not change. The authors conclude that CPAP at 10 cm H2O is the more effective technique, either because it allows relaxation of chest wall musculature on expiration, or because EPAP at 10 cm H2O increases chest wall muscle tone.

Acute Disease↗

Pulmonary function before and after prolonged continuous positive airway pressure by mask.

This investigation examined whether prolonged continuous positive airway pressure (CPAP) applied by face mask could sustain an increase in functional residual capacity (FRC). Before median sternotomy, nine adults performed multiple-breath nitrogen washout to determine FRC and spirometry. The day after operation, lung volumes were measured before and 10 min after the 4-h application of 7.5 cm H2O of CPAP with a mask. Mean FRC, forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and FEV1/FVC after CPAP were similar to pretreatment values. Although CPAP can restore FRC to preoperative values, and did increase FRC in these patients, FRC deteriorates within 10 min after CPAP is removed. Therefore, when a sustained increase in FRC is desired after median sternotomy, CPAP should be applied without interruption.

Critical Care↗

Lung mechanics and neuromuscular output during CO2 inhalation after airway anesthesia.

Airway anesthesia with aerosolized lidocaine has been associated with an increase in minute ventilation (VE) during CO2 inhalation. The increase in VE may be due to increased neuromuscular output or decreased mechanical load on breathing. To evaluate this we measured VE, breathing pattern, mouth occlusion pressure, and lung mechanics in 20 normal subjects during room-air breathing and then inhalation of 6% CO2-94% O2, before and after airway anesthesia. Measurements of lung mechanics included whole-lung resistance, dynamic and static compliance, and functional residual capacity. Airway anesthesia had no detectable effect on any measurements during room-air breathing. During CO2 inhalation, airway anesthesia produced increases in VE and mean inspiratory flow rate (VT/TI) and more negative inspiratory pleural pressure but had no detectable effect on lung mechanics or mouth occlusion pressure. Pleural pressure was more negative during the latter 25% of inspiration. We concluded that airway receptors accessible to airway anesthesia play a role in determining neuromuscular output during CO2 inhalation.

Adult↗

Mode of action of bronchodilating drugs on histamine-induced bronchoconstriction in asthmatic children.

The bronchodilatory response of three beta 2-agonists (fenoterol, salbutamol, and terbutaline), administered by a metered aerosol inhaler, was assessed in 19 asthmatic children after histamine-induced bronchoconstriction. At 1-min intervals, the changes in total pulmonary flow resistance (R1) and dynamic lung compliance (C dyn) were measured. After rank-ordering according to the base line value of C dyn (62 to 200% predicted), the patients were divided into two groups according to lung compliance: (1) patients with greater compliance (C dyn, 129 to 200% predicted) and (2) patients with lesser compliance (C dyn, 69 to 116% predicted). The effect of the three bronchodilators on the mean decrease of R1 and on the increase of C dyn was studied and analyzed for each drug separately. In all patients, salbutamol was the most efficient bronchodilator of small airways (P less than 0.02). The most striking feature of this beta 2-mimetic was observed in patients whose lungs were initially overinflated (functional residual capacity over 120% predicted) but not obstructed before the histamine challenge (P less than 0.005). In these subjects C dyn and R1 are normalized after inhalation of salbutamol. After fenoterol and terbutaline inhalation, obstruction of the large airways was not fully alleviated. In addition, these two drugs seemed not to affect the ventilatory asynchronism (C dyn alterations) in patients whose lungs had been overinflated before drug inhalation (C dyn again around 150% predicted).

Adolescent↗