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Ventilation inhomogeneities and mixed venous blood N2 in multibreath N2 washout.

The single path model of airway gas transport, with and without a distributed blood source term, was used to simulate multiple-breath N2 washout by breathing pure O2 in two lung models: a single-region lung model (SRLM) which produces series inhomogeneity, and a seven-region lung model (7RLM) incorporating both series and parallel inhomogeneities. Normalized phase III slopes (Sn) from N2 expirograms were computed for each breath and compared with published human experimental data obtained under similar conditions. The 7RLM predicts well the trend of experimental Sn N2 changes and is superior to the SRLM in the first part (the unsteady state), implying that this part of the curve is mostly due to convective mixing of the seven parallel flow streams. In the quasi-steady state, the 7RLM is not obviously superior to the SRLM. Functional residual capacity and pulmonary perfusion are shown to strongly affect the number of breaths required to reach the quasi-steady state. The anatomical dimensions that appear to be critical in SRLM are not as important in the 7RLM.

Computer Simulation↗

Hemodynamic and pulmonary changes after drainage of significant pleural effusions in critically ill, mechanically ventilated surgical patients.

PURPOSE: Our purpose was to study the effects of drainage of significant pleural effusions in mechanically ventilated patients in a surgical intensive care unit. METHODS: Twenty-two ventilated patients in the surgical intensive care unit of a tertiary care center over a 12-month period who developed a pleural effusion large enough to require drainage were studied prospectively. All patients underwent serial portable chest radiography in the upright or semiupright position; the radiographs were reviewed by a radiology attending. Pleural effusions were classified as small, moderate, or large. Moderate or larger effusions were drained using an 8- to 12-Fr pigtail catheter inserted at the bedside under ultrasound guidance. Hemodynamic and pulmonary parameters were collected before and after the fluid was drained. Parameters studied included those outlined in the physiologic profile and included measured and calculated physiologic variables, arterial blood gas measurements, and Svo2 measurements. Ventilator settings before and after were also recorded. RESULTS: Average initial pleural effusion drainage was 1,262 +/- 762 mL (range, 300-2,980 mL). Nine of the 22 patients had effusions drained from both the right and left chest. Blood pressure, systemic vascular resistance, Po2, Pco2, Svo2, Fio2, peak airway pressure, and spontaneous volume did not change significantly. Pulmonary capillary wedge pressure decreased (17.4 +/- 6.0 before, 13.6 +/- 4.4 after; p < 0.01), central venous pressure decreased (14.2 +/- 5.2 before, 11.5 +/- 4.4 after; p < 0.02), and pulmonary arteriovenous shunt decreased (26.7 +/- 15.1 before, 21.0 +/- 7.8 after; p < 0.04). Oxygen delivery increased (579.7 +/- 214.7 before, 662.8 +/- 263.3 after; p < 0.01) and oxygen consumption increased (146.3 +/- 61.6 before, 175.2 +/- 73.8 after; p < 0.01). Respiratory rate also decreased (19.4 +/- 6.5 before, 15.5 +/- 6.3 after; p < 0.05). There were no complications from the placement of the pigtail catheters. CONCLUSION: Drainage of pleural effusions results in increased oxygen delivery and oxygen consumption coinciding with a decrease in pulmonary capillary wedge pressure. The pulmonary arteriovenous shunt decreased, implying an increase in functional residual capacity and improved oxygenation. Further study is needed to determine whether these changes lead to an improved patient outcome (i.e., reduction in length of stay, ventilator days, or mortality).

Adolescent↗

Mechanical work on the lungs and work of breathing with positive end-expiratory pressure and continuous positive airway pressure.

The mechanical work on the lung required during spontaneous breathing with positive end-expiratory pressure (PEEP) was compared with different methods of continuous positive airway pressure (CPAP) in nine young healthy athletes (surfers) at levels of 5, 10, 15, and 20 cm H2O. At the level of 20 cm H2O, PEEP increased the mean total work per minute by 116 percent and the total work per liter by 121 percent. The percent increase rose linearly with the level of PEEP. In contrast, with methods of CPAP that maintained the airway pressure (Paw) constant, the total work per minute decreased by 45 per cent at a PEEP of 10 cm H2O and remained at this level with PEEP of 15 and 20 cm H2O. Use of PEEP did not increase the functional residual capacity (FRC) in these spontaneously breathing subjects. In contrast, CPAP resulted in a rise in FRC proportional to the level of CPAP. This suggests that CPAP must be applied in a manner that maintains Paw constant to provide optimal assistance to ventilation.

Adult↗

Relationship between regional lung volume and regional pulmonary vascular resistance.

We have examined the relationship between regional pulmonary vascular resistance (PVRr) and regional lung volume (VLr) to determine whether the decrease in blood flow in the dependent lung (zone 4) was related to lung volume. Regional blood flow (Qr) was measured with radiolabeled macroaggregates at functional residual capacity (FRC) and at transpulmonary pressure of 10 cmH2O (PL10) in 10 anesthetized supine dogs. VLr was determined at FRC by measuring lung density in frozen lung slices and was calculated at PL10 using each dog's pressure-volume curve. We found that when PVRr was expressed as a function of VLr there was not a single relationship between the two. Instead we found two separate U-shaped curves, one at FRC and one at PL10 indicating that the increased vascular resistance at the lung base remained when the lung volume was made uniform by inflation to PL10. This suggests that there is no simple relationship between VLr and PVRr.

Animals↗

Oxygen radicals in the nonvagal component of noncholinergic airway constriction.

To test the hypothesis that oxygen radicals play an important role in the nonvagal component of the noncholinergic bronchoconstriction in vivo, 37 guinea pigs weighing 329 +/- 8 g were randomly divided into five groups: group 1, vagotomy; group 2, vagotomy + CAT (catalase); group 3, vagotomy + SOD (superoxide dismutase); group 4, vagotomy + PBN (alpha-phenyl-N-tert-butyl nitrone); and group 5, capsaicin pretreatment. CAT, SOD, and PBN are antioxidants. Each animal was anesthetized, paralyzed, artificially ventilated, and pretreated with atropine and phenoxybenzamine. Immediately after acute capsaicin challenge, animals in group 1 exhibited decreases in maximal expiratory flow, dynamic respiratory compliance, and total lung capacity, as well as an increase in functional residual capacity, indicating noncholinergic airway constriction. The bronchoconstriction was significantly ameliorated by SOD and PBN, and it was almost abolished by capsaicin pretreatment. Thirty minutes after acute capsaicin challenge, there was a significant decrease in airway NEP activity and an increase in lung substance P level in group 1 but not in other groups. These results indicate that nonvagal component of noncholinergic bronchoconstriction is partially modulated by oxygen radicals.

Animals↗

Hyperinflation, trapped gas and theophylline in chronic obstructive pulmonary disease.

Assessment of patients with chronic airflow limitation traditionally involves the measurement of airway obstruction by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), as well as hyperinflation by residual volume (RV). Patients often claim reduction of breathlessness during theophylline therapy, without change of spirometry. In severe airflow limitation there is often a difference in lung volumes measured by helium dilution and plethysmography. The latter is thought to measure the absolute amount of gas in the lungs at functional residual capacity (FRC), whereas helium dilution measures only air in rapid communication with the mouth. The difference between the two is considered to represent poorly-ventilated areas of the lung, and is termed trapped gas volume. Twenty two patients with "irreversible" airflow limitation, mean (SD) FEV1 1.15 (0.52) l, FVC 2.57 (0.88) l, were studied. Uniphyllin Continus tablets (Napp Laboratories) were given at a dose to provide a mean steady-state plasma level of 14 mg.l-1, in a placebo-controlled, double-blind, cross-over study. The measurements made were FEV1, FVC, static lung volumes, 6 min walking distance (6WD), breathlessness after exercise assessed by visual analogue scales (VAB), and arterial blood gases. No significant correlation was found between changes in VAB and changes in RV measured by the helium dilution technique (RV (He)), FEV1 or FVC, but there were good correlations with trapped gas volume (r = 0.61, p < 0.01). The plethysmographic element of the calculated trapped gas volume reflects change in the sensation of breathlessness, and is affected by treatment with theophylline.

Aged↗

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↗

Lung volume, gas mixing, and mechanics of breathing in mechanically ventilated very low birth weight infants with idiopathic respiratory distress syndrome.

We assessed pulmonary function in 14 mechanically ventilated newborn very low birth weight infants with idiopathic respiratory distress syndrome by means of a face-out, volume displacement body plethysmograph and nitrogen washout analyses. Specially designed computer programs were used for calculations of lung volumes, ventilation, gas mixing efficiency, and mechanical parameters. In addition to very low compliance and moderately elevated resistance of the respiratory system, there were considerably impaired gas mixing efficiency and low functional residual capacity (FRC). No correlations between positive end-expiratory pressure and mean airway pressure versus compliance, resistance, or FRC could be found. Neither could correlations be found between FRC and compliance or FRC and the calculated right to left shunt.

Female↗

Breathing during exercise in subjects with mild-to-moderate airflow obstruction: effects of physical training.

In this study we explored the effects of physical training on the response of the respiratory system to exercise. Eight subjects with irreversible mild-to-moderate airflow obstruction [forced expiratory volume in 1 s of 85 +/- 14 (SD) % of predicted and ratio of forced expiratory volume in 1 s to forced vital capacity of 68 +/- 5%] and six normal subjects with similar anthropometric characteristics underwent a 2-mo physical training period on a cycle ergometer three times a week for 31 min at an intensity of approximately 80% of maximum heart rate. At this work intensity, tidal expiratory flow exceeded maximal flow at control functional residual capacity [FRC; expiratory flow limitation (EFL)] in the obstructed but not in the normal subjects. An incremental maximum exercise test was performed on a cycle ergometer before and after training. Training improved exercise capacity in all subjects, as documented by a significant increase in maximum work rate in both groups (P < 0.001). In the obstructed subjects at the same level of ventilation at high workloads, FRC was greater after than before training, and this was associated with an increase in breathing frequency and a tendency to decrease tidal volume. In contrast, in the normal subjects at the same level of ventilation at high workloads, FRC was lower after than before training, so that tidal volume increased and breathing frequency decreased. These findings suggest that adaptation to breathing under EFL conditions does not occur during exercise in humans, in that obstructed subjects tend to increase FRC during exercise after experiencing EFL during a 2-mo strenuous physical training period.

Adult↗

Treatment of adult asthma: controlled double-blind clinical trial of oxitropium bromide.

Sixteen young adult sufferers from extrinsic paroxysmal asthma with pollen hypersensitivity took part in a therapeutic trial of the synthetic anticholinergic agent oxitropium bromide administered by a metered dose inhaler. The study comprised three 3-week periods. The first, run-in period was carried out to confirm the ability of the patients to maintain a daily record of symptoms. During the second and third periods, the patient received 3 X 2 inhalations of drug or placebo in a cross-over design. The medical staff was blind to the nature of the aerosol (drug or placebo), which was given in random order. The run-in clinical score was high. Asymptomatic days were relatively infrequent and daily drug consumption was high. Functional studies between the cross-over periods showed flow-rate values close to normal, with an increase in residual volume and functional residual capacity. During treatment either with placebo or oxitropium, there was a statistically significant decrease in clinical scores. Results for oxitropium bromide treatment were significantly better than the run-in values (p less than 0.005) and the placebo period (p less than 0.02). There was no significant change in non-trial drug consumption. Functional values showed no difference in terms of flow rate, although oxitropium did cause a significant improvement in the RV/TLC ratio (p less than 0.05). No adverse reactions were reported.

Administration, Intranasal↗

Effects of breathing exercises on breathing patterns in obese and non-obese subjects.

Chest physiotherapy in connection with abdominal surgery includes different deep-breathing exercises to prevent post-operative pulmonary complications. The therapy is effective in preventing pulmonary complications, especially in high-risk patients such as obese persons. The mechanisms behind the effect is unclear, but part of the effect may be explained by the changes in breathing patterns. The aim of this study was therefore to describe and to analyse the breathing patterns in obese and non-obese subjects during three different breathing techniques frequently used in the treatment of post-operative patients. Twenty-one severely obese [body mass index (BMI) > 40] and 21 non-obese (BMI 19-25) subjects were studied. All persons denied having any lung disease and were non-smokers. The breathing techniques investigated were: deep breaths without any resistance (DB), positive expiratory pressure (PEP) with an airway resistance of approximately +15 cmH2O (1.5 kPa) during expiration, inspiratory resistance positive expiratory pressure (IR-PEP) with a pressure of approximately -10 cmH2O (-1.0 kPa) during inspiration. Expiratory resistance as for PEP. Volume against time was monitored while the subjects were sitting in a body plethysmograph. Variables for volume and flow during the breathing cycle were determined. Tidal volume and alveolar ventilation were highest during DB, and peak inspiratory volume was significantly higher than during PEP and IR-PEP in the group of obese subjects. The breathing cycles were prolonged in all techniques but were most prolonged in PEP and IR-PEP. The functional residual capacity (FRC) was significantly lower during DB than during PEP and IR-PEP in the group of obese subjects. FRC as determined within 2 min of finishing each breathing technique was identical to before the breathing manoeuvres.

Adult↗

Regional ventilation in statically and dynamically hyperinflated dogs.

Using the parenchymal marker technique in normal anesthetized dogs, we compared the dynamics of regional lung expansion between two ventilation strategies designed to increase mean thoracic volume. Dynamic hyperinflation (DH was produced by ventilating the lungs at a rate of 50 breaths/min and with a duty cycle of 0.5. Static hyperinflation (SH) was produced through the application of extrinsic positive end-expiratory pressure while the lungs were ventilated at a rate of 15 breaths/min and with a duty cycle of 0.15. Regional tidal volume (VT,r), regional functional residual volume, and the time delay between regional expansion and the flow signal at the common airway were computed for up to 100 regions/lobe in 5 animals. Ventilation strategy had no effect on the overall variance of VT,r within lobes. Although the VT,r measured during SH correlated with VT,r measured during DH, the average correlation coefficient was only 0.69. Ventilation rate-related differences in VT,r and regional functional residual capacity varied with the regional time delay in ways qualitatively consistent with parallel inhomogeneity of unit time constants. However, a large component of frequency-dependent behavior remains unexplained by established mechanisms. We conclude that DH and SH should not be considered equivalent lung unit recruitment strategies.

Animals↗

Mechanical and chemical damage to lung tissue caused by meconium aspiration.

We investigated the effects of meconium on the lungs of an adult rabbit model to distinguish between mechanical obstruction of airways and chemical pneumonitis. After the rabbits were anesthetized and intubated, 20% human meconium in saline was instilled into the trachea. Arterial and mixed venous blood gases, functional residual capacity, cardiac output vascular pressures, calculated venous admixture, and pulmonary vascular resistance were measured. Sections of affected lung tissue were examined microscopically. The results were consistent with an early mechanical obstruction of airways with gradual development of chemical pneumonitis over 48 hours.

Airway Obstruction↗

Relationship of symptoms to lung function abnormalities in preterm infants at follow-up.

Recurrent respiratory symptoms are common in preterm infants in the first 2 years of life. The aim of this study was to determine the lung function abnormalities associated with such symptoms. Forty preterm infants, with a median gestational age of 29 weeks were studied at a median postnatal age of 12 months. Twenty-two suffered from recurrent symptoms, defined as wheezing and/or coughing on at least 4 days per week over the previous month. Lung function was assessed by measurement of functional residual capacity (FRC), using a helium gas dilution technique, and airway resistance (Raw) and thoracic gas volume (TGV) plethysmographically. No significant difference was found in TGV between symptomatic and asymptomatic infants, but the median FRC was lower (P less than 0.01), Raw higher (P less than 0.01), and FRC:TGV ratio lower (P less than 0.001) in the symptomatic infants. These lung function abnormalities in the symptomatic infants are suggestive of gas trapping.

Airway Resistance↗

The effects of body fat on pulmonary function and gas exchange in cynomolgus monkeys.

Obesity adversely affects lung function in humans often reducing arterial blood oxygenation. To determine if obesity adversely affects lung function in cynomolgus monkeys, which is a species that is often used for pulmonary research, pulmonary mechanics, ventilation, functional residual capacity (FRC), and arterial blood gases were measured using spontaneous respiration and on mechanical ventilation with room air or 100% O(2). Body fat percentage was measured by dual energy X-ray absorption. Blood leptin levels were measured by radioimmune assay. Obese monkeys breathed faster with lower tidal volume, but pulmonary resistance and dynamic lung compliance did not change with body fat. FRC and blood leptin were, respectively, negatively and positively correlated with percent body fat. FRC correlated moderately with ventilatory parameters and strongly with arterial oxygen tension, alveolar-arterial oxygen difference and venous admixture. Therefore, obesity in cynomolgus monkeys had marked, deleterious effects on FRC, ventilation and arterial oxygenation. Obesity may be an important confounding variable in lung function studies in primates.

Animals↗

Effect of surgical lung volume reduction on respiratory muscle function in pulmonary emphysema.

Lung volume reduction surgery (LVRS) in patients with severe lung emphysema restores the thoracic configuration to a more normal functional capacity. The aim of this study was to investigate whether reduction in intrathoracic volume by LVRS improves the inspiratory muscle force generation of the respiratory pump. Pulmonary function tests, maximal inspiratory mouth pressure (MIP), sniff nasal inspiratory pressure (SNIP), sniff transdiaphragmatic pressure (Pdi), and inspiratory mouth occlusion pressure (P0.1) were measured in 17 emphysematous patients (mean (+/- SEM) age 53 +/- 2 yrs) before and 1 month after LVRS. The mean value of forced expiratory volume in one second (FEV1) increased (0.82 +/- 0.07 vs 1.12 +/- 0.08 L; p < 0.0001), whilst there was a decrease (p < 0.0001) in residual volume (RV) (337 +/- 31 vs 250 +/- 21 % of predicted), functional residual capacity (FRC) (210 +/- 9 vs 159 +/- 9% pred), and total lung capacity (TLC) (138 +/- 6 vs 110 +/- 5% pred). The mean value of MIP increased by 52% from 4.8 +/- 0.4 to 7.3 +/- 0.6 kPa (p < 0.001), the mean value of SNIP increased by 66% from 3.9 +/- 0.4 to 6.5 +/- 0.5 kPa (p < 0.001), and the mean value of Pdi increased by 28% from 6.0 +/- 0.6 to 7.7 +/- 0.8 kPa (p < 0.05) after LVRS. P0.1 decreased on average by 24% from 0.46 +/- 0.03 to 0.35 +/- 0.02 kPa after LVRS. No significant correlations were found between inspiratory muscle (MIP, SNIP, Pdi) and respiratory drive (P0.1) indices, lung function data, 6 min walk distance, or dyspnoea score. In conclusion, the observed clinical improvement of patients with severe emphysema after lung volume reduction surgery results, in part, from an increased ability of the inspiratory muscles to generate force, which is paralleled by a significant decrease in central respiratory drive.

Adult↗

Exhaled nitric oxide in severe obesity: effect of weight loss.

Exhaled nitric oxide (NO) is a recognized biomarker in the lower respiratory tract. The effect of large variation in body mass on exhaled NO in the same individuals is not well known. The aim of the study was to evaluate both the effect of severe obesity and the influence of weight reduction on exhaled NO. A consecutive series of 24 uncomplicated obese patients (OB), who had laparoscopic adjustable gastric banding (LAGB) and 15 healthy controls (HC) were studied. Body mass index (BMI), exhaled NO and respiratory function tests were assessed. Exhaled NO was lower in obese in comparison to HC (12.0+/-3.6ppb versus 15.8+/-4.0ppb, p=0.0035). A significant positive correlation was found between exhaled NO and BMI in HC, which was not evident in OB. Among the respiratory indexes, functional residual capacity was significantly associated to exhaled NO. After 1 year, 12 obese patients undergone to LAGB were re-evaluated. Mean BMI (kg/m(2)) decreased from 44.8 before surgery to 32.3 post-operatively. The exhaled NO increased from 11.8+/-3.2ppb before surgery to 14.9+/-3.1ppb 1 year post-operatively (p=0.0023, n=12). In conclusion exhaled NO is consistently reduced in severe obesity and it is restored after weight reduction. The relationship between exhaled NO, large body mass excess and decrease of resting lung volume in severe obesity deserves further studies.

Adult↗

Obesity, smooth muscle, and airway hyperresponsiveness.

Both asthma and obesity are large and growing public health issues. Mounting evidence now implicates obesity as a major risk factor for asthma, thus linking these 2 major epidemics. Moreover, both in human subjects and in mice, obesity appears to predispose toward airway hyperresponsiveness. This review describes potential mechanisms whereby obesity might modify airway smooth muscle function to explain these observations. These mechanisms include both static and dynamic mechanical factors attributable to decreases in functional residual capacity and decreases in tidal volume that are observed in the obese. They include also obesity-related changes in lung development, chronic systemic inflammation (including increased serum levels of inflammatory cytokines and chemokines), and adipocyte-derived factors, including leptin, adiponectin, and plasminogen activator inhibitor.

Adiponectin↗