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Effects of cyclo-oxygenase inhibition on ozone-induced respiratory inflammation and lung function changes.

Inhalation of O3 causes airways neutrophilic inflammation accompanied by other changes including increased levels of cyclo-oxygenase products of arachidonic acid in bronchoalveolar lavage fluid (BALF). Ozone O3 exposure also causes decreased forced vital capacity (FVC) and forced expiratory volume after 1 s (FEV(1)), associated with cough and substernal pain on inspiration, and small increases in specific airway resistance (SRAW). The spirometric decrements are substantially blunted by pretreatment with indomethacin. Since the O3-induced decrement in FVC is due to involuntary inhibition of inspiration, a role for stimulation of nociceptive respiratory tract afferents has been suggested and cyclo-oxygenase products have been hypothesized to mediate this stimulation. However, the relation (if any) between the O3-induced neutrophilic airways inflammation and decreased inspiratory capacity remains unclear. We studied the effects of pharmacologic inhibition of O3-induced spirometric changes on the inflammatory changes. Each of ten healthy men was exposed twice (5-week interval) to 0.4 ppm O3 for 2 h, including 1 h of intermittent exercise (ventilation 601*min(-1)). One-and-a-half hours prior to and midway during each exposure the subject ingested 800 mg and 200 mg, respectively, of the non-steroidal anti-inflammatory drug ibuprofen (IBU), or placebo [PLA (sucrose)], in randomized, double-blind fashion. Spirometry and body plethysmography were performed prior to drug administration, and before and after O3 exposure. Immediately following postexposure testing, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed. Neither IBU nor PLA administration changed pre-exposure lung function. O3 exposure (with PLA) caused a significant 17 percent mean decrement in FEV(1) (P <0.01) and a 56 percent increase in mean SRAW. Following IBU pretreatment, O3 exposure induced a significantly lesser mean decrement in FEV(1) (7 percent) but still a 50 percent increase in mean SRAW. IBU pretreatment significantly decreased post-O3 BAL levels of prostaglandin E2 (PGE2) by 60.4 percent (P <0.05) and thromboxane B(2) (TxB(2)) by 25.5 percent (P <0.05). Of the proteins, only interleukin-6 was significantly reduced (45 percent, P <0.05) by IBU as compared to PLA pretreatment. As expected, O3 exposure produced neutrophilia in BALF. There was, however, no effect of IBU on this finding. None of the major cell types in the BALF differed significantly between pretreatments. We found no association between post-exposure changes of BALF components and pulmonary function decrements. We conclude that IBU causes significant inhibition of O3-induced increases in respiratory tract PGE(2) and TxB(2) levels concomitant with a blunting of the spirometric response. This is consistent with the hypothesis that the products of AA metabolism mediate inhibition of inspiration. However, IBU did not alter the modest SRAW response to O3.

Adult↗

Exercise training decreases ventilatory requirements and exercise-induced hyperinflation at submaximal intensities in patients with COPD.

STUDY OBJECTIVES: We hypothesized that endurance exercise training would reduce the degree of hyperinflation for a given level of exercise and thereby improve submaximal exercise endurance. METHODS: Twenty-four patients with COPD (mean FEV(1), 36.4 +/- 8.5% of predicted [+/- SD]) undertook a high-intensity cycle ergometer exercise training program for 45 min, three times a week for 7 weeks. Before and after training, the patients performed both an incremental exercise test to maximum and a constant work rate (CWR) test on a cycle ergometer at 75% of the peak work rate obtained in the pretraining incremental test. Ventilatory variables were measured breath-by-breath, and inspiratory capacity (IC) was measured every 2 min to assess changes in end-expiratory lung volume. RESULTS: After training, the increase in peak oxygen uptake was not statistically significant; however, the peak work rate increased by 12.9 +/- 10.3 W (p < 0.01). For the CWR test performed at the same work rate both before and after training, ventilation and breathing frequency (f) were lower after training (average, 1.97 L/min and 3.2 breaths/min, respectively; p < 0.01) and IC was greater (by an average of 133 mL, p < 0.05), signifying decreased hyperinflation. The increase in IC at the point of termination in the shortest CWR test for each individual (defined as isotime) correlated well with both the decreased f (r = 0.63, p = 0.001) and with the increase in CWR exercise endurance (average, 13.1 min, r = 0.46, p = 0.023). CONCLUSIONS: Exercise training in patients with severe COPD dramatically improves submaximal exercise endurance. Decreased dynamic hyperinflation may, in part, mediate the improvement in exercise endurance by delaying the attainment of a critically high inspiratory lung volume.

Aged↗

Muscle sympathetic vasoconstrictor activity in hydrocortisone-induced hypertension in humans.

AIM: This study was undertaken to test the hypothesis that increased sympathetic vasomotor drive is responsible for cortisol-induced hypertension. METHODS: Ten healthy male subjects on a fixed sodium diet (150 mmol/day) were randomized to five days of treatment with cortisol (200 mg/day) or placebo in a double-blind crossover study. On day 5 of each treatment, multi-unit muscle sympathetic activity was recorded from the common peroneal nerve. Resting muscle sympathetic activity (MSA) was measured in the recumbent position and stimulated MSA was measured in the final 20 sec of end-inspiratory capacity apnoea and end-expiratory apnoea and in the second minute of a cold pressor stimulus. A subgroup of six subjects also underwent identical MSA measurements following 5 days treatment with dexamethasone (3 mg/day). MAJOR FINDINGS: Cortisol, but not placebo, significantly increased systolic (115+/-2 vs 129+/-3 mmHg precortisol vs cortisol day 5, p < 0.001) and diastolic blood pressure (53+/-3 vs 61+/-3, p < 0.05). Resting MSA was significantly reduced by cortisol (23.9+/-2.3 to 5.0+/-2.0 bursts/min, placebo vs cortisol, p < 0.01). Cortisol significantly attenuated the increase in MSA observed at end-inspiratory apnoea (56.3+/-3.9 vs 35.4+/-6.6, p < 0.05) and end-expiratory apnoea (50.5+/-3.5 vs 26.3+/-6.2 bursts/min, n = 8, p < 0.05), and during the cold pressor response (55.0+/-12.7 vs 21.4+/-7.6, n = 5, p < 0.05). Dexamethasone significantly increased systolic blood pressure and suppressed resting and stimulated MSA. No changes in body weight, haematocrit or angiotensin II concentrations occurred during dexamethasone treatment. CONCLUSION: MSA is significantly suppressed by cortisol treatment. As suppression of MSA is also observed during treatment with the pure glucocorticoid dexamethasone, suppressed MSA cannot be attributed to increased plasma volume or to changes in angiotensin II concentration. We conclude that cortisol-induced hypertension is not due to increased muscle sympathetic vasomotor drive.

Adult↗

Effect of continuous positive airway pressure on forced expiratory flows in infants with tracheomalacia.

Continuous positive airway pressure (CPAP) is used to minimize airway collapse in infants with tracheomalacia. Forced expiratory flows (FEFs) at functional residual capacity (FRC) increase with increasing CPAP in infants with tracheomalacia, and it has been suggested that CPAP prevents airway collapse by "stenting" the airway open. Since FEF is greater at higher than at lower lung volumes, we evaluated whether the increase in flow measured at FRC (V FRC) with CPAP could be explained by the increase in FRC with CPAP. We measured full FEF-volume curves at CPAP levels of 0, 4, and 8 cm H2O in six infants with tracheomalacia and five healthy control infants. In both groups of infants, FVC did not change with CPAP; however, inspiratory capacity (IC) decreased and thus FRC increased with increasing CPAP. FEFs at FRC increased with increasing levels of CPAP; however, the FEFs at 50% and 75% of expired volume were not different for the three levels of CPAP for both groups of infants. Our finding that FEFs measured at the same lung volumes did not differ for the different levels of CPAP indicates that CPAP affects forced flows primarily by increasing lung volume.

Forced Expiratory Flow Rates↗

Expiratory flow limitation and orthopnea in massively obese subjects.

BACKGROUND: Morbidly obese subjects, who often complain about breathlessness when lying down, breathe at low lung volume with a reduced expiratory reserve volume (ERV). Therefore, during tidal breathing the expiratory flow reserve is decreased, promoting expiratory flow limitation (EFL), which is more likely to occur in the supine position, when the relaxation volume of the respiratory system, and hence the functional residual capacity (FRC), decrease because of the gravitational effect of the abdominal contents. PURPOSE: The aim of the study was to assess EFL and orthopnea in massively obese subjects and to evaluate whether orthopnea was associated with the development of supine EFL. METHODS: In 46 healthy obese subjects (18 men) with a mean (+/- SD) age of 44 +/- 11 years and a mean body mass index (BMI) of 51 +/- 9 kg/m(2), we assessed EFL in both the seated and the supine positions by the negative expiratory pressure method and assessed postural changes in FRC by measuring the variations in the inspiratory capacity (IC) with recumbency. Simultaneously, dyspnea was evaluated in either position using the Borg scale dyspnea index (BSDI) to determine the presence of orthopnea, which was defined as any increase of the BSDI in the supine position. RESULTS: Partial EFL was detected in 22% and 59%, respectively, of the overall population in seated and supine position. The mean increase in the supine IC amounted to 120 +/- 200 mL (4.1 +/- 6.4%), indicating a limited decrease in FRC with recumbency in these subjects. Orthopnea, although mild (mean BSDI, 1.7 +/- 1.3), was claimed by 20 subjects, and in 15 of them EFL occurred or worsened in the supine position. Orthopnea was associated with lower values of seated ERV (p < 0.05) and was marginally related to supine EFL values (p = 0.07). No significant effect of age, BMI, obstructive sleep apnea-hypopnea syndrome, FEV(1), and forced expiratory flow at 75% of vital capacity was found on either orthopnea or EFL. CONCLUSION: In morbidly obese subjects, EFL and dyspnea frequently occur with the subject in the supine position, and both supine EFL and low-seated ERV values are related to orthopnea, suggesting that dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure may be partly responsible for orthopnea in massively obese subjects.

Adult↗

Control of breathing patterns and abdominal muscles during graded loads and tilt.

Tilting from supine to upright purportedly enhances both segmental and pulmonary proprioceptive feedback, whereas an expiratory threshold load (ETL) preferentially enhances pulmonary feedback. To test this we studied 13 adults when supine and 60 degrees and 90 degrees head up. We measured tidal volume, inspiratory duration (TI), and expiratory duration (TE) from flow; estimated end-expiratory lung volume from inspiratory capacity; and determined burst amplitudes and durations from abdominal electromyograms (EMGs). ETLs were incremented from 0 (control) to 25 cmH2O in 5-cmH2O steps. Tidal volume was significantly increased by ETL but was unaffected by body position. Every load prolonged TE, whereas TI remained unchanged. When subjects were supine, abdominal EMGs were silent but became tonically active when subjects were upright. During ETL, abdominal activity became rhythmical and phase locked to expiration. Bursts amplitudes were enhanced with each increment in ETL, but burst durations did not change even though TE was prolonged. The altered breathing pattern and active expiration augmented inspiratory flow and decreased end-tidal PCO2. Responses were greatest when subjects were 90 degrees head up. The load-related increments in abdominal recruitment, with no change in burst durations, fit the concept of two central pattern generators: one controlling pattern and the other controlling rhythm of the central respiratory drive.

Abdominal Muscles↗

Reproducibility of the alternating breath test of fractional inspired O2 in infants.

We conducted a reproducibility study of the alternating breath test (ABT) for assessing peripheral chemoreceptor function in infants. The ABT delivers a rapid hypoxic stimulus to the peripheral chemoreceptors with breath-by-breath alternations of the inspired O2 fraction. The reproducibility of the ABT performed on a single occasion has not been extensively studied in infants. Eight unsedated infants (postnatal age, 22+/-19 d; weight, 3.2+/-0.4 kg) were studied in standardized conditions: morning naps, supine position, room temperature 22-24 degrees C, quiet sleep, and face mask attached to a pneumotachograph connected to a two-way electric valve. Respiratory gases were analyzed by mass spectrometer. Two ABTs were performed. Each included a 2-min control run (CR) alternating between air and air, and a 2-min test run (TR) alternating between air and 0.15 O2. After data preprocessing, on average 13+/-11% of the data were rejected because of sighs, apneas, and cycles with the fraction of inspired oxygen above 0.17. Using the remaining validated breaths, the response to ABT was calculated for the CR, for all breaths in the TR (TR(T)), and for the first 50 breaths of the TR (TR50). During the ABTs oxygen saturation did not fall below 96%, and heart rate was not affected. Inspired and end-tidal CO2 fractions remained unchanged during the ABTs. FetO2 oscillated in TRs at a lower values than in CRs and differed significantly between breaths of air and hypoxic breaths of TRs. All infants responded to ABT with percentage alternation coefficients of TRs significantly greater than those of CRs for all respiratory variables. The values of the coefficients were not significantly different between both ABT, and between TR50 and TR(T). The greatest values of the coefficients were for timing variables compared with flows and volume. We conclude that the ABT is a reproducible test of peripheral chemoreceptor function under standardized conditions.

Breath Tests↗

Impact of a physical rehabilitation program on the respiratory function of adolescents with idiopathic scoliosis.

BACKGROUND: Idiopathic adolescent scoliosis (AIS) causes not only spinal deformities but rib cage abnormalities that lead to abnormal volumes and pulmonary capacity on pulmonary function testing (PFT). The objective of this study was to analyze the impact of a physical rehabilitation program on respiratory function in surgical patients with AIS. METHODS: From October 2003 to October 2004, a total of 34 patients (age range, 10 to 18 years) presenting with AIS and a thoracic curvature between 45 degrees and 88 degrees were studied prospectively at a tertiary academic hospital. The patients underwent clinical and radiographic evaluations of the vertebral deformity, chest radiographs, PFT, evaluation of peak expiratory flow, and 6-min walk tests (6MWTs) before and after joining a physical rehabilitation program for 4 months. RESULTS: An improvement in FVC, inspiratory capacity, FEV(1), expiratory reserve volume, and performance assessed by 6MWT were observed after rehabilitation. CONCLUSIONS: Global conditioning improved after the rehabilitation program. This was expressed by both PFT and 6MWT results.

Adolescent↗

Mechanical advantage of the canine diaphragm.

The mechanical advantage (mu) of a respiratory muscle is defined as the respiratory pressure generated per unit muscle mass and per unit active stress. The value of mu can be obtained by measuring the change in the length of the muscle during inflation of the passive lung and chest wall. We report values of mu for the muscles of the canine diaphragm that were obtained by measuring the lengths of the muscles during a passive quasistatic vital capacity maneuver. Radiopaque markers were attached along six muscle bundles of the costal and two muscle bundles of the crural left hemidiaphragms of four bred-for-research beagle dogs. The three-dimensional locations of the markers were obtained from biplane video-fluoroscopic images taken at four volumes during a passive relaxation maneuver from total lung capacity to functional residual capacity in the prone and supine postures. Muscle lengths were determined as a function of lung volume, and from these data, values of mu were obtained. Values of mu are fairly uniform around the ventral midcostal and crural diaphragm but significantly lower at the dorsal end of the costal diaphragm. The average values of mu are -0.35 +/- 0.18 and -0.27 +/- 0.16 cmH2O. g-1. kg-1. cm-2 in the prone and supine dog, respectively. These values are 1. 5-2 times larger than the largest values of mu of the intercostal muscles in the supine dog. From these data we estimate that during spontaneous breathing the diaphragm contributes approximately 40% of inspiratory pressure in the prone posture and approximately 30% in the supine posture. Passive shortening, and hence mu, in the upper one-third of inspiratory capacity is less than one-half of that at lower lung volume. The lower mu is attributed primarily to a lower abdominal compliance at high lung volume.

Animals↗

Functional residual capacity and body position in the dog.

Resting lung volumes in the supine position (FRCs) were determined by N2 washout method in 67 dogs under pentobarbital anesthesia and computed in ml/kg body weight (BW). In 21 other dogs, FRCs and the change in FRC from the supine to upright positions (deltaFRC) were determined; these lung volumes were expressed in ml/kg BW and in percentage of TLC40 (lung volume at 40 cmH2O positive-pressure inflation). It was found that a) FRCs averaged 38.6 plus or minus 8.2 and 42 plus or minus 5.9 ml/kg BW in the two groups of dogs; b) deltaFRC averaged 23 plus or minus 4 ml/kg BW resulted in large data dispersion, a large coefficient of variation (CV) and a poor correlation (r) of lung volume to BW; D) on the contrary, marked uniformity of FRCs and FRCu (upright FRC) was obtained by expressing the resting lung volumes in %TLC40, allowing an accurate prediction of FRC from the inspiratory capacity (IC). Relationship of FRCu to TLC was comparable to human data reported in the literature. FRCs (%TLC40) was smaller than values previously reported for awake human subjects, probably due to the FRCs reduction in our dogs by anesthesia.

Animals↗

Impact of surgically-induced weight loss on respiratory function: a prospective analysis.

BACKGROUND: Morbid obesity (MO) causes several degrees of respiratory impairment that may resolve after weight reduction. The aims of the present study were to investigate the frequency of respiratory impairment in a selected cohort of morbidly obese patients with BMI 40-50 kg/m(2) with no respiratory symptoms and to evaluate the impact of surgically-induced weight loss on respiratory function. METHODS: Prospective analysis of respiratory impairment was conducted before surgery and 1 year after surgery in a cohort of patients with MO who underwent vertical banded gastroplasty (VBG). 30 consecutive patients with MO who underwent VBG (14 open and 16 laparoscopic) in a 1-year period were studied. Respiratory function tests, arterial blood gases and hemoglobin were obtained in all patients before and 1 year after VBG. RESULTS: Results were analyzed using the Wilcoxon signed-rank test and Spearman for variables without normal distribution. Mean age was 35+/-8 years; there were 3 males and 27 females. BMI was 44+/-4 kg/m(2) before surgery and 32+/-4 kg/m(2) at 1-year follow-up. By respiratory function tests, the diagnosis of obstructive disease was made before surgery in 4 patients and a restrictive disorder was identified in 4 additional patients. Evidence of pulmonary disease was absent in all patients 1 year after surgery. Forced vital capacity, inspiratory and expiratory forces, tidal volume, SaO(2), and PaCO(2) significantly improved after weight reduction. CONCLUSION: Surgically-induced weight loss significantly improves pulmonary function.

Adult↗

Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD.

STUDY OBJECTIVES: We have previously shown that tiotropium at 18 mug reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. The present study was designed to gain further insight into the duration of improvements. DESIGN, PATIENTS, AND INTERVENTIONS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted in 261 COPD patients (mean age, 62.5 +/- 7.4 years [+/- SD]; 189 men and 72 women; mean FEV1, 1.2 +/- 0.4 L [43 +/- 12.7% predicted]). On day 0 (first dose), day 21, and day 42 of treatment, pulmonary function tests were performed before and 1 h 20 min after dosing, followed by a constant work rate cycle ergometry test (75% maximum work capacity) to symptom limitation at 2.25 h after dosing. On day 42, an additional constant work rate cycle ergometry test was performed at 8 h after dosing. RESULTS: Adjusted mean (+/- SE) endurance time (ET) on day 42 was 803 +/- 40 s (tiotropium), vs 568 +/- 42 s (placebo) at 2.25 h after dosing (primary end point; treatment difference, 236 +/- 58 s; p = 0.0001) and 665 +/- 40 s (tiotropium) vs 494 +/- 42 s (placebo) at 8 h after dosing (treatment difference, 171 +/- 58 s; p = 0.0035). Adjusted mean dyspnea intensity at isotime on day 42 was 4.60 +/- 0.16 Borg units (tiotropium), vs 5.65 +/- 0.16 Borg units (placebo) at 2.25 h after dosing (p < 0.001), and 5.54 +/- 0.17 Borg units (tiotropium) vs 6.51 +/- 0.18 Borg units (placebo) at 8 h after dosing (p < 0.001). Adjusted mean pre-exercise inspiratory capacity (IC) on day 42 was 2.41 +/- 0.03 L (tiotropium) vs 2.19 +/- 0.03 L (placebo) at 2.25 h after dosing (p < 0.001), and 2.31 +/- 0.03 L (tiotropium) vs 2.16 +/- 0.03 L (placebo) at 8 h after dosing (p < 0.001). The significant increase in IC with tiotropium compared with placebo was maintained throughout exercise. CONCLUSIONS: The present study confirms that tiotropium reduces lung hyperinflation at rest and during exercise, reduces exertional dyspnea, and improves symptom-limited exercise tolerance in COPD patients. Furthermore, this study shows that this improvement is present at 2.25 h and at 8 h after dosing after 6 weeks of treatment.

Aged↗

Breathing pattern and occlusion pressure during moderate and heavy exercise.

We studied changes in breathing pattern and mouth occlusion pressure (P0.1) in 11 healthy subjects performing graded steady-state exercise on a cycle ergometer up to the maximal load sustainable for 4 min. With increasing work intensity both the tidal volume (VT) and end-inspiratory volume relations to inspiratory (TI) and expiratory (TE) durations were linear in the moderate work load range; in the high load range VT and end-inspiratory volume tended to plateau with further decreases in TI and TE. The ratio of TI to total breath duration (TI/Ttot) increased with work intensity. Intraindividual coefficients of variation for VT, breathing frequency (f), mean inspiratory flow (VT/TI), and other respiratory variables decreased with increasing work intensity, indicating that breath-to-breath variations in breathing pattern became smaller as the level of ventilation increased. P0.1 rose with VT/TI as a power function with an exponent averaging 1.5 (range 1.3-1.9), indicating that the ratio P0.1/(VT/TI), an index of respiratory system impedance, increased with VT/TI and work intensity. We conclude that in moderate and heavy exercise the work of inspiration at a given ventilation is reduced because of the increase in TI/Ttot, the impedance of the respiratory system increases with work intensity because of both an increase in f and a flow-dependent rise in airway resistance, and the neuromuscular inspiratory activity is reflexly augmented because of internal flow-resistive loading.

Adult↗

Pulmonary function after successful heart transplantation. One year follow-up.

Congestive heart failure (CHF) has been associated with the development of restrictive ventilatory abnormalities and decreased pulmonary diffusing capacity. Whether these physiologic changes reflect permanent alterations of lung anatomy or result solely from potentially reversible alterations of lung water is not known. To examine this issue, we reviewed the pulmonary function tests (PFTs) and cardiac catheterization data from recipients of successful heart transplants prior to and 1 year after transplantation. Thirty-eight patients met the inclusion criteria (median age, 52 years). The median duration of symptomatic CHF prior to transplantation was 22 months (range, 3 to 72 months). After transplantation, spirometry revealed an improvement in FEV1 from 75.8 +/- 3.5 to 99.1 +/- 2.8 percent of predicted and FVC from 81.3 +/- 3.7 to 101.6 +/- 3.0 percent of predicted (p < 0.001). The FEV1/FVC ratio remained unchanged at 80 percent. Nonsmokers and former smokers had similar improvements in spirometry after transplantation. The TLC improved from 91.1 +/- 3.3 to 105.5 +/- 2.9 percent of predicted (p < 0.001); this improvement was due to an increase in inspiratory capacity. Diffusing capacity for carbon monoxide was decreased before transplantation and showed a small decline after transplantation from 82.3 +/- 3.2 to 76.8 +/- 2.6 percent of predicted (p < 0.05). After correction of severe CHF by cardiac transplantation, normalization of FEV1, FVC, and TLC can be anticipated. Diffusing capacity, however, may actually decline after transplantation.

Adolescent↗

[Hemodynamic side effects of high-frequency jet ventilation as a function of lung volume. Impedance spirometric studies].

In five patients with acute respiratory insufficiency the changes in tracheal pressure (P), lung volume (V) and transthoracic electric impedance TEI (Z) were measured during delayed expiration all over the inspiratory capacity (IC) from TLC to FRC. The quasi-static V/Z- and Z/P-curves were two-dimensionally displayed, and the Z/P-curve was volume-calibrated on the Y-axis (Z) using the linear V/Z-relationship. During high-frequency jet ventilation (HFJV, 200/min), the Z- and P-excursions were displayed on the "frozen" Z/P-curve as flat discs. By well-aimed increase in driving pressure and I/E-ratio the unknown FRC was enhanced in 4 stages (I-IV) by 0.33 IC, 0.5 IC, 0.66 IC and 0.75 IC, to measure haemodynamic reactions 10 minutes later (Swan-Ganz catheter). The pulmonary vascular resistance remained unchanged between stage I and II. It changed moderately in stage III (+14%) and was found to be markedly increased in stage IV (+45%). The increase in PVR was well parabolically correlated (r = 0.88) to the fraction of IC by which FRC was expanded. In a previous study a very similar function could be documented by us for the end-inspiratory lung volume during conventional PEEP ventilation. Concomitant to the increase in PVR the CI fell linearilly (r = 0.95). We conclude from our results: 1. TEI may be of value in monitoring HFJV. It offers the possibility to measure the increase in lung volume ("PEEP effect") and to titrate it deliberately within the usable volume range IC. 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiography, Impedance↗

Breathing pattern and neuromuscular drive during CO2 rebreathing in normal man and in patients with COPD.

In 11 normal subjects and in 10 patients with chronic obstructive pulmonary disease we evaluated breathing pattern and mouth occlusion pressure (PO.1), while breathing room air and during reinhalation of a hypercapnic hyperoxic gas mixture. In the breathing pattern we analyzed the time and volume components of the respiratory cycle: tidal volume (VT), inspiratory time (Ti), expiratory time (Te), total time of respiratory cycle (Ttot); mean inspiratory flow (VT/Ti) and Ti/Ttot ratios, respiratory frequency (RF) and instantaneous ventilation (VE). In the normal subjects, increase in VE during rebreathing mainly depended on an increase in both VT and VT/Ti without significant changes in Ti. During CO2 rebreathing the patients exhibited a lesser increase in VE compared to normals, due to a lesser increase in VT. However, expressing VT in percent of resting inspiratory capacity showed that VT attained at the end of rebreathing (VTmax) was similar to that noted in the normal subjects at the same minute of rebreathing. Furthermore, percent increase in VE, VT, VT/Ti and PO.1 between resting value and that at 56 mm Hg (delta %), were significant in both groups with a major increase in the normal subjects for VE and VT/Ti. In comparison, delta % decreases in both Te and Ttot were found to be significant only in the normal subjects. VT/Ti was related to VE in a similar way in the two groups. In contrast, in the normal subjects, Ti/Ttot did not increase with increasing VE. During rebreathing increase in PO.1 was found to be similar in the normal subjects and in patients. However, for a given neuromuscular drive VE and VT/Ti were greater in the normal subjects than in the patients. These data show that in the patients as a whole no significant changes in breath intervals occur during CO2 rebreathing. Furthermore, in patients, in spite of a similar increase in neuromuscular drive, the efficiency by which inspiratory muscle output (PO.1) is converted into VT/Ti was found to be reduced.

Adult↗

Six-minute walking test in cystic fibrosis adults with mild to moderate lung disease: comparison to healthy subjects.

The six-minute walking test (6MWT) has been widely utilized to evaluate global exercise capacity in patients with cystic fibrosis. The aim of this study was to assess the exercise capacity by 6MWT, measuring four outcome measures: walk distance, oxygensaturation and pulse rate during the walk, and breathlessness perception after the walk, in a group of cystic fibrosis adults with mild to moderate lung disease, and in healthy volunteers, as the control group. Moreover, the study examined the relationship between 6MWT outcome measures and pulmonary function in patients. Twenty-five adults (15 females, age range 18-39 years) with cystic fibrosis and 22 healthy volunteers (14 females, age range 20-45 years) performed a 6MWT following a standard protocol. Walk distance, oxygen saturation (SpO2) and pulse rate at rest and during walk, and breathlessness perception after walk assessed by visual analogue scale (VAS) were measured. Cystic fibrosis patients did notdiffer from healthy volunteers in walk distance (626 +/- 49 m vs. 652 +/- 46 m) and pulse rate. Patients significantly differed from healthy volunteers in SPO2 during the walk (mean SpO2) (P < 0.0001) and VAS (P < 0.0001). In patients, SPO2 during the walk significantly correlated with forced expiratory volume in 1 sec (FEV1) (P < 0.0001), residual volume (RV) (P < 0.001), resting SPO2 (base SpO2) (P < 0.001), and inspiratory capacity (IC) (P < 0.01). In addition, VAS significantly correlated with resting SPO2 (P < 0.01) and IC (P < 0.01). On the basis of regression equations by stepwise multiple regression analysis, SpO2 during walk was predicted by FEV1 (r2 = 0.60) and VAS by IC (r2 = 0.31), whereas walk distance was not reliably predicted by any assessed variables. This study showed that cystic fibrosis adults with mild to moderate lung disease covered a normal walk distance with unimpaired cardiac adaptation, but experienced a significant fall in oxygen saturation and an increased breathlessness perception during exercise. Resting pulmonary function was related to oxygen saturation and breathlessness perception during walk, but contributed significantly only tothe prediction of oxygen saturation. We suggest that 6MWT could be valuable for identifying patients who might experience oxygen desaturation and dyspnoea during demanding daily activities.

Adolescent↗

Dyspnea, ventilatory pattern, and changes in dynamic hyperinflation related to the intensity of constant work rate exercise in COPD.

STUDY OBJECTIVE: We undertook the present study to investigate the perception of dyspnea (with respect to changes in end-inspiratory and end-expiratory lung volumes), during four different levels of high-intensity constant work rate exercise (CWRE) in patients with severe COPD. DESIGN: Crossover descriptive study with consecutively recruited subjects. SETTING: Tertiary university hospital. PATIENTS: Twenty-seven subjects with severe COPD (mean [+/- SD] age, 65 +/- 5 years of age; mean FEV1, 43 +/- 8% predicted; and mean inspiratory capacity [IC]; 74 +/- 14% predicted). MEASUREMENTS AND RESULTS: Subjects randomly performed four high-intensity CWRE tests (conducted at 65%, 75%, 85%, and 95% of their symptom-limited peak work rate). Dyspnea, leg fatigue, and IC were determined every 2 min during exercise with breath-by-breath gas exchange and ventilatory measurements. There was a good correlation between the resting IC percent predicted and the oxygen uptake (V(O2)) peak (r = 0.64 to 0.69 between the IC percent predicted and V(O2) peak at the four work rates). There were significant differences (p < 0.01) in mean respiratory rate (33 +/- 6, 35 +/- 6, 37 +/- 6, and 38 +/- 6 min), peak dyspnea score (5.9 +/- 1.3, 6.3 +/- 1.4, 6.8 +/- 1.2, and 6.9 +/- 1.6), minute ventilation (45.0 +/- 8.7, 43.8 +/- 7.7, 43.1 +/- 8.7, and 42.8 +/- 8.0 L/min), leg fatigue (4.8 +/- 1.3, 5.1 +/- 1.3, 5.7 +/- 1.4, and 5.8 +/- 1.4), and end-tidal carbon dioxide partial pressure (4.41 +/- 0.36, 4.53 +/- 0.33, 4.66 +/- 0.31, and 4.76 +/- 0.24 kPa), respectively, for tests conducted at 65%, 75%, 85%, and 95% of their symptom-limited peak work rate, and in mean end-expiratory lung volume ([EELV] 4.55 +/- 0.44, 4.69 +/- 0.43, and 4.79 +/- 0.43 L), respectively, for tests conducted at 65%, 75%, and 85% of their symptom-limited peak work rate. In multivariable analysis, the factors that were independently correlated with dyspnea (p < 0.05) were EELV, peak inspiratory flow, and leg fatigue/discomfort. CONCLUSION: In COPD subjects with flow limitation at rest, the perception of dyspnea increased nonlinearly with the magnitude of high-intensity CWRE in association with a faster respiratory pattern and an increase in EELV. At the highest work rates, it appeared that a reduction in tidal volume and ventilation peak may have limited the tolerance to exercise.

Aged↗