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Evidence of airway obstruction in children with idiopathic scoliosis.

Restrictive pulmonary function abnormalities are reported in children and adolescents with idiopathic scoliosis. We hypothesized that spirometry alone, without more extensive testing, including the measurement of lung volumes, is inadequate in characterizing lung function in these children and may miss obstructive abnormalities including significant gas trapping. To examine this hypothesis, we reviewed the pulmonary function tests of 44 children (36 female, 8 male) between the ages of 10 and 18 years with idiopathic scoliosis prior to surgical correction. Spirometry, measurements of lung volumes with both plethysmographic and helium dilution techniques, and bronchodilator response were analyzed for evidence of reversible airway obstruction and gas trapping. Eighteen of 44 (41%) subjects had significant restriction. Only 3 (7%) subjects met standard criteria for airflow obstruction. However, 20 (46%) subjects had an elevated total gas volume by plethysmography-functional residual capacity by helium dilution ratio indicative of moderate or severe gas trapping, 10 (23%) subjects showed mild gas trapping, 8 (18%) subjects had a ratio suggestive of gas trapping, and only 6 (14%) subjects were normal. Additionally, significant improvement in airway mechanics was noted after bronchodilator administration. Specific conductance improved in all subjects, with a mean increase of 62% +/- 8.0 (p<0.001). The residual volume-total lung capacity ratio and total gas volume by plethysmography also decreased significantly (mean decrease, 22.5% +/- 3.0 and 15% +/- 1.0, respectively, p<0.001) in response to inhaled bronchodilators. In conclusion, although restrictive defects are commonly present in children with idiopathic scoliosis, significant gas trapping and responses to bronchodilators also commonly occur. These abnormalities may be missed without extensive pulmonary function testing.

Adolescent↗

Does lung growth occur when mature lobes are transplanted into children?

Lung volume increases after living donor lobar lung transplantation (LD) in children. The mechanism responsible for this increase may be alveolarization (lung growth) or alveolar dilation. The diffusing capacity of the lung for carbon monoxide adjusted for lung volume (DLco/VA) should decrease if alveolar dilation occurs, but not if lung growth occurs. Pulmonary function tests were measured 1-12 months after transplant in 20 children receiving LD transplants and in 11 children receiving cadaveric whole lung transplantation (CL). One month after transplant there were no differences between LD and CL recipients in age, gender, or height. Compared to the first month after transplant, height increased at 6-12 months after LD (p < 0.05), and only at 12 months after CL (p = 0.02). Total lung capacity (TLC) showed an 11-22% increase at 3-12 months after LD, and an 11-14% increase at 6-12 months after CL. DLco/VA showed an 11-17% decrease at 3-12 months after LD. However, in recipients of CL, DLco/VA showed a transient decrease of 10% at 3-6 months post-transplant, but was not significantly lower at 9-12 months. LD recipients had lower DLco/VA values than CL recipients at 6-12 months after transplant (p < 0.05). We conclude that following LD, lung volume increases, but DLco/VA decreases. We speculate that alveolar dilation, rather than alveolarization, is the primary mechanism of increased lung volume in children following LD.

Adolescent↗

Tracking variations in airway caliber by using total respiratory vs. airway resistance in healthy and asthmatic subjects.

An index of airway caliber can be tracked in near-real time by measuring airway resistance (Raw) as indicated by lung resistance at 8 Hz. These measurements require the placing of an esophageal balloon. The objective of this study was to establish whether total respiratory system resistance (Rrs) could be used rather than Raw to track airway caliber, thereby not requiring an esophageal balloon. Rrs includes the resistance of the chest wall (Rcw). We used a recursive least squares approach to track Raw and Rrs at 8 Hz in seven healthy and seven asthmatic subjects during tidal breathing and a deep inspiration (DI). In both subject groups, Rrs was significantly higher than Raw during tidal breathing at baseline and postchallenge. However, at total lung capacity, Raw and Rrs became equivalent. Measured with this approach, Rcw appears volume dependent, having a magnitude of 0.5-1.0 cmH2O. l-1. s during tidal breathing and decreasing to zero at total lung capacity. When resistances are converted to an effective diameter, Rrs data overestimate the increase in diameter during a DI. Simulation studies suggest that the decrease in apparent Rcw during a DI is a consequence of airway opening flow underestimating chest wall flow at increased lung volume. We conclude that the volume dependence of Rcw can bias the presumed net change in airway caliber during tidal breathing and a DI but would not distort assessment of maximum airway dilation.

Adult↗

Lung volume reference values for blue collar workers not exposed to occupational respiratory hazards.

Epidemiologic research into occupationally related lung disease often requires the comparison of a study group with an external nonexposed comparison group. In order to develop such an external comparison group, blue collar workers, who had no obvious adverse occupational pulmonary exposure, performed simple spirometry, were administered a standard questionnaire, and had standard posterior-anterior and lateral chest radiographs taken. Prediction equations were established for three indices of lung volume, namely total lung capacity, residual volume, and their ratio, for various combinations of race, sex, and smoking groups. Asymptomatic non-smokers with normal radiograph results were then extracted from the overall group, and separate prediction equations were established. The relationship between age and total lung capacity is discussed.

Adult↗

Bronchoscopic lung volume reduction using tissue engineering principles.

Bronchoscopic lung volume reduction (BLVR), a minimally invasive procedure based on tissue engineering principles, was performed in six sheep with papain-induced experimental emphysema (EMPH). Physiologic measurements, at baseline, after generation of EMPH, and at 3 and 9 weeks after BLVR, included lung volumes, diffusing capacity (DL(CO)), pressure-volume relationships for the lung and chest wall, pleural pressures generated during active respiratory muscle contraction, lung resistance and dynamic elastance. The animal model displayed hyperinflation (change in total lung capacity +8%; change in residual volume +66%), reduced DL(CO) (-21%), and elevated airway resistance (+76%) that resembled advanced human EMPH. BLVR was well tolerated without complications, and it reduced lung volumes (change in total lung capacity -16%; change in residual volume -55%) in a pattern that resulted in significant improvements in vital capacity (10%). At autopsy, well-organized, peripheral scars associated with tissue contraction were observed at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung, reduced overall lung volume, and improved respiratory function safely and consistently. The BLVR technology employed in this study addresses the limitations identified in our prior attempt at BLVR therapy and appears safe and effective enough to justify a trial in humans.

Airway Resistance↗

A comparison of two methods for measuring airway distensibility: nitrogen washout and the forced oscillation technique.

The measurement of airway stiffness is an important tool for studying airway remodelling in asthma. The relationship between airway calibre and lung volume (airway distensibility) was measured by forced oscillation technique (FOT) and compared with that measured by single-breath nitrogen washout (SBNW). In four non-asthmatic healthy subjects and three asthmatics, anatomical dead space (VDF) was measured by SBNW and respiratory system conductance (Grs) was measured by FOT at 6 Hz. During SBNW testing, 0.51 oxygen boluses were inhaled from three different lung volumes: functional residual capacity (FRC), 11 above FRC and near total lung capacity (TLC). Following inhalation of the oxygen bolus subjects exhaled to residual volume and then inhaled to TLC. During FOT, subjects breathed 0.5-1.01 tidal volumes but with gradually increasing end-expiratory lung volume until close to TLC, then returned to normal breathing before inhaling to TLC. This was also repeated but with reducing lung volume from TLC. Absolute lung volumes were measured by body plethysmography and related to volumes during FOT and SBNW by reference to TLC obtained at the end of each SBNW or FOT test manoeuvre. Distensibility was calculated as the linear regression slopes of VDF or Grs versus lung volume. Distensibility measured by VDF ranged 16-37 ml 1(-1) lung volume and by Grs it ranged 0.06-0.19 1 s(-1) cmH2O(-1) 1(-1) lung volume. Both distensibility measurements were correlated (Pearson's R2 = 0.91, p = 0.001). The SBNW and FOT are comparable methods for measuring airway distensibility and may have similar clinical usefulness. However, further studies are required to make any specific inferences about the relationship between airway distensibility by FOT and airway remodelling.

Administration, Inhalation↗

Pathophysiology of congenital diaphragmatic hernia II: the fetal lamb CDH model is surfactant deficient.

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and pulmonary hypertension. We hypothesize that a surfactant deficiency may in part be contributing to the pathophysiology of CDH. This study documents the functional, quantitative, and qualitative aspects of the surfactant status of the alveolar air-liquid interface and the type II pneumocyte in the fetal lamb CDH model. Ten lamb fetuses (gestational age, 80 days) had a CDH created via a left thoracotomy and then were allowed to continue in utero development until term. Three litter mates and three nonoperated time-dated fetuses served as controls. At term, pressure-volume curves were performed to measure pulmonary compliance and total lung capacity. Alveolar lavage was then performed to measure the quantitative and the qualitative aspects of pulmonary surfactant. Finally, isolation of type II pneumocytes allowed quantification of phospholipid synthesis. When compared with controls (N = 6), the CDH lambs (N = 5) had significantly smaller lungs (P = .009), decreased total lung capacity (P less than .001) and compliance (P less than .001), reduced total lavaged phospholipids (P = .006), and decreased percent phosphatidylcholine (P = .02). CDH lambs also had increased total lavaged proteins (P = .05) and higher minimum dynamic surface tension (P less than .001). A surfactant deficiency may be contributing to the pathophysiology of CDH. Surfactant replacement therapy in premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Exogenous surfactant may also benefit infants with CDH.

Animals↗

Changes in lung mechanics induced by acute isocapnic hypoxia.

We measured lung mechanics in seven healthy males during acute isocapnic hypoxia (PAO2 = 40-50 Torr; PACO2 = 38-42 Torr). Hypoxia was accompanied by increases in total lung capacity (mean increase +/- SD; 0.40 +/- 0.24 liters; P less than 0.005) functional residual capacity (0.34 +/- 0.25 liters; P less than 0.01) and residual volume (0.56 +/- 0.44 liters; P less than 0.02) in all subjects. Specific conductance of the lung decreased during hypoxia (P less than 0.02). The static deflation pressure-volume curve of the lung was shifted upward during hypoxia in all subjects. Resting end-expiratory recoil pressure of the lung was slightly, but not significantly lower during hypoxtic expiratory lung compliance was greater during hypoxia (0.39 +/- 0.04 l/cmH2O) than control measurements (0.31 +/- 0.05 l/cmH2O; P less than 0.005). No change was noted in dynamic lung compliance. All changes in lung mechanics were reversed within three minutes of reoxygenation. We conclude that acute isocapnic hypoxia increases total lung capacity in man and suggest that this may be due to the effect of hypoxia on the airways and pulmonary circulation.

Adult↗

The effect of hyperinflation on rib cage-abdominal motion.

Abnormalities of rib cage-abdominal motion are common in patients with chronic obstructive pulmonary disease (COPD), but the basis of the abnormal motion has not been completely determined. Although airway obstruction has been shown to be a major factor in causing abnormal chest wall motion, the effect of hyperinflation (which has numerous adverse effects on respiratory muscle function) has not been systematically examined. We induced graded levels of hyperinflation in six healthy volunteers using continuous positive airway pressure (CPAP) levels of 10, 20, and 30 cm H2O. Chest wall motion was measured by a calibrated inductive plethysmograph. Rib cage-abdominal asynchrony and paradox were quantitated by the Konno-Mead method of analysis. CPAP levels of 10, 20, and 20 cm H2O produced increases in end-expiratory lung volume of 0.98 +/- 0.14 (SE), 1.90 +/- 0.31, and 2.42 +/- 0.37 L, respectively (p < 0.0001). This corresponded to an increase in the ratio of functional residual capacity to predicted total lung capacity from 0.38 +/- 0.08 at baseline to 0.74 +/- 0.14 at 30 cm H2O CPAP-comparable to that seen in patients with COPD. Hyperinflation induced an increase in inspiratory abdominal paradox, 1.0 +/- 0.7% at baseline versus 3.6 +/- 1.7% at 30 cm H2O (p < 0.05), but this is unlikely to be clinically significant. A significant increase in asynchrony or rib cage paradox did not develop with hyperinflation. In conclusion, the primary factor contributing to abnormal chest wall motion in patients with COPD is likely to be increased airway resistance, and hyperinflation makes only a minor contribution.

Abdomen↗

Comparison of the single breath with the intrabreath method for the measurement of the carbon monoxide transfer factor in subjects with and without airways obstruction.

BACKGROUND: Measurement of the carbon monoxide transfer factor (TLCO) has traditionally been performed using the single breath method but recently the intrabreath method has been developed. The aim of this study was to compare the two methods in the clinical evaluation of patients with obstructive and non-obstructive pulmonary disorders. METHODS: Measurements of TLCO with the intrabreath method were carried out on a study sample composed of 50 patients with non-obstructive disorders and 50 with airways obstruction (FEV1/FVC < 70%) either before or after a single breath measurement of the TLCO had been performed. The method involves the continuous analysis of a single slow expirate using a computerised rapid multigas infrared analyser. TLCO, alveolar volume (VA), TLCO/VA, and inspired vital capacity (IVC) values were obtained for both groups by both methods. RESULTS: When measured with the intrabreath method the group with airways obstruction showed lower TLCO and TLCO/VA values than the non-obstructive group. VA was higher in both patient groups when measured with the intrabreath technique. The same test also showed higher TLCO values with the intrabreath method in the group with non-obstructive disorders and lower TLCO/VA values with the intrabreath method in those with airways obstruction. The corresponding parameters obtained by the two methods correlated closely, with no correlation between the magnitude of the differences with the magnitude of the readings. An index of gas mixing indicated a better distribution of the inspired air for the intrabreath method than for the single breath method. The VA values obtained with the intrabreath method showed a closer agreement to the actual total lung capacities measured by body plethysmography. CONCLUSION: The intrabreath method of determining TLCO is comparable to the traditional single breath method. Measurement of alveolar volume by the intrabreath method approximates more closely to total lung capacity, even in subjects with airways obstruction.

Adult↗

Maximal shortening of inspiratory muscles: effect of training.

Normal subjects can increase their vital capacity by appropriate training. We tested whether that change can be achieved by greater maximal shortening of the inspiratory muscles without concomitant increases in peak static inspiratory pressures. Sixteen healthy volunteers participated in the study: eight were randomly assigned to make 20 inhalations to total lung capacity, held for 10 s with the glottis open, each day for 6 wk; the remainder served as nontraining controls. Before and after the 6-wk study period, we made multiple determinations of lung volumes and of curves relating lung volume to maximal static inspiratory (and expiratory) pressure. Control subjects had no significant changes from base line in any variable. In the training group, the mean vital capacity increased 200 +/- 74 ml (P less than 0.05) or 3.9 +/- 1.3% (P less than 0.02), without a significant change in residual volume. After training, the mean maximal inspiratory pressure at the airway opening (PI) at a lung volume equal to the base-line total lung capacity was 27 +/- 8 cmH2O in this group (vs. zero before training; P less than 0.02). Values of PI in the mid-vital capacity range did not change. We conclude that in response to appropriate training stimuli inspiratory muscles can contract to shorter minimal lengths, a capacity potentially important in progressive pulmonary hyperinflation.

Adolescent↗

Pulmonary pressure- volume relationships after corticotropin (ACTH) and salin injections in fetal rabbits.

ACTH mixed with barium sulfate injected into fetal rabbits on day 24 of a 31-day gestation was associated with increased lung maturity compared with lungs of noninjected controls when assessed by deflation pressure-volume curves and lung weight to body weight ratios measured on day 27. Fetuses injected with saline and barium sulfate also had accelerated (although somewhat less) lung maturation, perhaps from an ACTH-mediated response to stress. The ACTH group LA) maintained the largest lung volumes on deflation, followed by the saline group (B), the ACTH controls (C), and the saline controls (D). Volumes (percentage of total lung capacity) between the two injected groups and their controls (A versus C; B versus D) were significantly different at transthoracic pressures of 15, 10, 7, 4, 0, and -2 cm water (p less than 0.05). Volumes (percentage of total lung capacity) between the ACTH group and the saline group (A versus B) and between the two controls groups (C versus D) were not significantly different. Wet lung weight to body weight ratios were significantly different between the injected groups and their respective controls, between the two injected groups, and between the two control groups.

Adrenocorticotropic Hormone↗

Determinants of restrictive lung function in asbestos-induced pleural fibrosis.

We evaluated whether restrictive lung function among asbestos-exposed individuals with pleural fibrosis was caused by radiographically inapparent parenchymal inflammation and/or parenchymal fibrosis. All 24 study participants were sheet metal workers who were nonsmokers with normal parenchyma on posteroanterior chest radiograph. These subjects had either normal pleura (n = 7), circumscribed plaques (n = 9), or diffuse pleural thickening (n = 8). After controlling for age, years in the trade, and pack-years of smoking, we found that sheet metal workers with diffuse pleural thickening had a lower forced vital capacity (P less than 0.001), total lung capacity (P less than 0.01), and CO-diffusing capacity of the lung (P less than 0.05) than those with normal pleura. Similarly, sheet metal workers with circumscribed plaques were found to have a reduced forced vital capacity; however, because of the small number of study subjects, this difference (regression coefficient = -11.0) was only marginally significant (P = 0.06). Although circumscribed plaque and diffuse pleural thickening were both associated with a lymphocytic alveolitis and a higher prevalence of parenchymal fibrosis on high-resolution computerized tomography (HRCT) scan, neither a lymphocytic alveolitis nor the finding of parenchymal fibrosis on HRCT scan influenced the relationship between pleural fibrosis and restrictive lung function. We conclude that pleural fibrosis is associated with restrictive lung function and abnormally low diffusion that appears to be independent of our measures of parenchymal injury (chest X-ray, bronchoalveolar lavage, and HRCT scan).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Radiographic (ILO) readings predict arterial oxygen desaturation during exercise in subjects with asbestosis.

BACKGROUND: Exercise impairment is common in subjects with asbestosis. Arterial oxygen desaturation during exercise is an important contributor to exercise limitation. The International Labour Office (ILO) classification of plain chest radiographs correlates with resting pulmonary function, but its value in predicting abnormal ventilatory responses to exercise, including desaturation, has not been explored. AIMS: To determine in subjects with asbestosis (1) if radiographic profusion scores and the extent of small irregular shadows on plain chest radiographs correlate with resting lung function and abnormal ventilatory responses to exercise; and (2) if radiographic scores add value to resting lung function tests in predicting abnormal ventilatory responses to exercise. METHODS: Thirty eight male subjects with asbestosis were included. Plain chest radiographs were read according to the ILO classification independently by three observers. All subjects underwent assessment of lung function and an incremental exercise test. RESULTS: Profusion scores and number of affected zones correlated significantly with the percentage predicted values of single breath diffusing capacity (DLCO), forced vital capacity (FVC), and total lung capacity (TLC). Arterial oxygen desaturation occurred in 29% of the subjects. The severity of desaturation correlated significantly with profusion and the number of affected zones. The combined use of number of affected zones, FEV(1)/FVC ratio and DLCO predicted desaturation during exercise with an explained variance of 41%. VO(2)max was significantly related only to DLCO but was not predicted by the ILO score. CONCLUSION: Arterial oxygen desaturation correlated with the profusion and extent of parenchymal abnormality on chest radiographs. The addition of morphological indices to physiological measurements is valuable for predicting oxygen desaturation during exercise but not for VO(2)max. Refinement of the radiographic scoring system and the addition of more sophisticated imaging techniques may further improve the predictive power.

Aged↗

Respiratory muscle force and ventilatory function in adolescents.

In 94 girls and 90 boys, aged 12.5-20.3 yr, the relationship of respiratory pressures or forces with lung volumes and ventilatory flows was studied. There was great variability in respiratory muscle performance, which helps to explain differences in lung volumes between individuals. Respiratory muscle force increases almost proportionally with thoracic dimensions, so that inspiratory and expiratory pressures generated at the level of residual volume (RV), functional residual capacity (FRC) and total lung capacity (TLC) are approximately constant with age. In the oldest boys there is evidence that the continued increase in lung volumes when they stop growing is due to a 'muscularity effect'. Boys generate larger pressures than girls at all lung volumes. Thus boys attain a larger TLC, and in spite of narrower airways, the same peak expiratory flow and a larger FIV1/FVC ratio than girls. Effort independent flows (FEV1 and MMEF), however, are larger in girls.

Adolescent↗

Diaphragm length during tidal breathing in patients with chronic obstructive pulmonary disease.

Diaphragm function is compromised in severe chronic obstructive pulmonary disease (COPD) by hyperinflation, but its ability to shorten and contribute to tidal volume is uncertain. We estimated coronal diaphragm length by measuring zone of apposition length with ultrasound and rib cage diameters with magnetometers, in 10 male patients with severe COPD and 10 age- and sex-matched control subjects. Diaphragm length was 20% shorter in patients at residual volume (413 and 536 mm in patients and control subjects, respectively) and FRC (381 and 456 mm, respectively), but was not different at total lung capacity (312 and 336 mm, respectively). Zone of apposition length was reduced 50% at residual volume and FRC in patients, but was larger at a given absolute lung volume than in control subjects. There were no differences in tidal volume (0.8 L), tidal changes in zone of apposition length (20 mm) and diaphragm length (38 and 42 mm), and tidal volume displaced by the diaphragm (0.6 L), even though mean FRC in patients was similar to predicted total lung capacity. Although the diaphragm is shorter at FRC in patients with COPD, its motion and change in length during tidal breathing is similar to that in control subjects.

Aged↗

The effects of intravenous infusion of saline on lung density, lung volumes, nitrogen washout, computed tomographic scans, and chest radiographs in humans.

In this study we examined the effect of a 15% increase in extracellular fluid volume on lung density, lung volumes, nitrogen washout, chest radiographs and computerized tomographic (CT) scans of the thorax in 5 volunteers. The objective of the study was to determine the sensitivity of these techniques in detecting small changes in lung water. Lung density was measured by a gamma ray Compton scatter technique and with an Ohio nuclear delta 2020 CT scanner. We measured or derived functional residual capacity, residual volume (RV), vital capacity (VC), and total lung capacity by helium dilution. Single-breath nitrogen washout was used to measure closing volume and the slope of phase III nitrogen washout (delta N2). Chest radiographs were taken in the posteroanterior and lateral projections. With the CT scanner we obtained slices 1 cm thick through the bases of the lungs and at 6 and 12 cm up from the bases. All these measurements were made before and 20 to 90 min after the intravenous infusion of 30 ml/kg body weight of warm saline over a period of 20 min. The most striking findings were a 24% increase in delta N2, a 14% increase in RV, and a 4.5% decrease in VC. Chest radiographs and the CT scans showed an increase in the size of the azygos veins. There was no change in Compton scatter density or the CT numbers. These results suggest that (1) tests of small airway function, such as RV and delta N2, are more sensitive than radiographic techniques to small increases in lung water, (2) there is some protection of the lung to increases in extracellular fluid volume.

Adult↗

Lung-volume reduction surgery for diffuse emphysema: radiologic assessment of changes in thoracic dimensions.

Patients with severe, diffuse emphysema may be candidates for pneumectomy (lung-volume reduction surgery, LVRS) to improve lung and respiratory muscle function. To identify candidates who might benefit from this surgery, it is necessary to understand how lung volumes and respiratory function are effected. In this article, the authors demonstrate a significant difference in lung size on chest radiographs obtained before and after surgery. Thirty-five of 71 consecutive patients undergoing LVRS had both preoperative and postoperative chest radiographs and pulmonary function tests available for retrospective review. Preoperative and postoperative measurements of lung height, transthoracic diameters, mediastinal width, heart size, diaphragmatic arc, and intercostal spaces were compared using paired t-tests. Radiographic measurements where also correlated with changes in lung volumes as measured by pulmonary function tests. Lung heights (right, left, mean lateral) and coronal diameter at the aortic arch were reduced after surgery (all p < 0.05). Forced vital capacity, forced expiratory volume in 1 second (FEV1), and vital capacity increased, and total lung capacity and residual volume decreased after surgery (all p < 0.05). Left lung height showed a significant correlation (p = 0.025) with FEV1; all other correlations between radiographic changes and pulmonary function test changes were not significant. The explanation for improved lung function in patients after LVRS is not completely clear and is probably multifactorial. Radiologic alterations reflect anatomic changes caused by surgery and support the theory that modifications of chest wall configuration occur and are likely responsible, in part, for improved symptomatology and respiratory function.

Adult↗