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Contribution of vagal afferents to breathing pattern in rats with lung fibrosis.

In anesthestized male Wistar rats with bleomycin-induced lung fibrosis we examined the influence of lung vagal non-myelinated and myelinated afferents in setting breathing pattern. Fourteen days after intratracheal instillation of bleomycin, lung compliance, total lung capacity (TLC) and inspiratory capacity were reduced while functional residual capacity and residual volume were increased. Baseline tidal volume (VT) was decreased and frequency (fR) increased in the bleomycin treated rats compared with controls. Selective vagal C-fiber blockade did not affect fR or VT in any group. Vagotomy resulted in an increase in VT and decrease in fR in both groups with the percent increase in VT/TLC and decrease in fR being significantly greater in the bleomycin rats compared with controls. Vagotomy also attenuated the significantly elevated PCO2 in the bleomycin treated rats suggesting that bleomycin-induced alterations in breathing pattern contribute to blood gas abnormalities. We conclude that vagal myelinated afferents contribute to the rapid shallow breathing in bleomycin treated rats.

Animals↗

The ventilatory response to arm elevation of patients with chronic obstructive pulmonary disease.

Although arm activity is poorly tolerated by patients with COPD, the ventilatory response to arm elevation alone is not well understood. We therefore studied the ventilatory response to arm elevation using a customized arm support sling to eliminate the effect of an increase in metabolic activity that might be attributable to independent arm elevation and used leg exercise to increase metabolic activity. During arm elevation at rest, there was a significant decrease in vital capacity (180 ml) and a small decrease in functional residual capacity (120 ml) as measured by body plethysmography. Minute ventilation was unchanged. When supported arm elevation (SAE) was compared with the control arm position (CAP), minute ventilation was unchanged although the pattern of breathing became more rapid and shallow (mean +/- SD, SAE vs CAP: fb = 17.9 +/- 5.3 vs 16.2 +/- 4.8 breaths.min-1; VT = 533 +/- 126 vs 579 +/- 142 ml; p < 0.05). During steady-state leg exercise, the increase in VO2, VCO2 and VE did not differ between SAE and CAP; however, both fb and VT changed toward a more rapid, shallow pattern of breathing (SAE vs CAP: fb = 24.3 +/- 3.0 vs 22.8 +/- 3.5 breaths.min-1; VT = 990 +/- 293 vs 1,081 +/- 309 ml; p < 0.05). During unsupported arm elevation VO2, VCO2, and VE, and fb were significantly greater than during the CAP. Approaches that train arm muscles and strategies that either support arm muscles or allow for frequent rests during upper arm activity may improve the endurance and the quality of life for COPD patients.

Aged↗

Lung function, maximum and submaximum exercise testing in COPD patients: reproducibility over a long interval.

This study was designed to investigate the reproducibility and clinical relevance of several lung function and exercise test indices in a sample of patients with stable severe chronic obstructive pulmonary disease (COPD). Twenty subjects (ages 67.8 +/- 2.0 years, forced expiratory volume in 1s, [FEV1] 39.7 +/- 2.8% predicted) receiving conventional medical therapy and pulmonary rehabilitation were tested 4 times at 1 month intervals. Testing procedures included lung function (inspiratory vital capacity [IVC], FEV1, plethysmographic functional residual capacity [FRC], specific conductance of the airways (sGaw), single breath transfer factor divided by the alveolar volume [TL/VA]); incremental, progressive, symptom-limited, cycle exercise (maximum work load [Wmax], maximum heart rate [HRmax], maximum ventilation [VEmax], maximum oxygen uptake [VO2max]); and 2 modes of submaximum exercise (12 min walking test [12 MWD] and endurance cycle test). The mean of the absolute value of the individual patient, session-to-session, variation was found to be 0.131 for FEV1, 102 ml/min for VO2max. The within-subject variability was the smallest for HRmax and IVC (mean intrasubject coefficient of variation, [CV intra] 5.0 and 6.5%) and the greatest for TL/VA, the work performed during the endurance cycle test (EW) and sGaw (CV intra 16.5, 19.4, and 22.7%), while it was reasonably low (8.1-10.2%) for all the other variables studied. Calculation of the F ratio of the intersubject variance to the residual (total minus intersubject) variance, interpreted as a signal-to-noise, ratio, yielded the following, in decreasing order: TL/VA, EW, VEmax, VO2max, IVC, FEV1, HRmax, Wmax, sGaw, 12 MWD, FRC. If we assume that a useful variable should combine a low within-subject variability (CV intra less than or equal to 10%) with a high signal-to-noise ratio, we conclude that, among all the variables studied, IVC, FEV1, VEmax, and VO2max are those with the greatest clinical potential for functional assessment in patients with COPD.

Aged↗

Acromegalic pneumonomegaly: lung growth in the adult.

Lung size was evaluated with pulmonary function tests in 10 patients with acromegaly, 1 pituitary giant, and 1 patient who had acromegaly but now has hypopituitarism. In the six acromegalic men all lung volumes were increased. The average values and per cent of predicted were total lung capacity 9.1 liters. 139%; functional residual capacity 5.2 liters, 145%; vital capacity 6.0 liters, 134%; and tissue volume 1.1 liters. There was no evidence of airflow obstruction or air trapping. Anatomic dead space was increased in proportion to the large lung volumes. Lung compliance was increased, averaging 0.43 liters/cm H(2)O, but lung elastic recoil was normal. These studies show that the lung is involved in the general visceromegaly of acromegaly and that lung size increases in acromegalic men as a result of actual lung growth. Despite the large lung volumes, diffusing capacity was normal suggesting that lung growth resulted from an increase in the size rather than from an increase in the number of alveoli. In contrast to the acromegalic men, lung volumes, anatomic dead space and tissue volume were normal in four acromegalic women, suggesting that sex hormones may modify the effect of growth hormone on the lung. Lung size was large in the pituitary giant but lung volumes were normal according to predicted values based on the patient's great height. Lung volumes were normal in the one male who had been acromegalic but who has been hypopituitary for 21 yr. The role of growth hormone in normal postnatal lung growth and in the maintainance of normal lung size remains to be defined.

Acromegaly↗

Safety and efficacy of alinidine in symptom-free asthmatics.

Alinidine is a new bradycardic agent which has been shown to be beneficial in the treatment of coronary heart disease. Patients with both coronary heart disease and obstructive lung disease are difficult to treat, because the use of beta-blockers in them is greatly limited by their potential to provoke bronchospasm. Alinidine has no beta-blocking, muscarinic or quinidine-like properties. In a randomized double-blind cross-over study the heart rate reducing effect and safety of alinidine 40 mg p.o. has been examined in 12 symptom-free asthmatics. Alinidine significantly reduced mean heart rate from 81 +/- 10.5 beats/min to 65 +/- 9.7 beats/min two hours after administration. Forced expiratory volume in one second (FEV1), vital capacity (CV), airway resistance (Raw), functional residual capacity (FRC), and specific airway conductance (SGaw) were not affected. It is concluded that alinidine did not influence respiratory function in patients with bronchial hypersensitivity.

Adult↗

Neonatal chest wall suspension splint: a novel and noninvasive method for support of lung volume.

Surfactant and musculoskeletal immaturity results in lower compliance of the lung relative to the chest wall, with clinical manifestations of low lung volume, marked chest wall retractions (CWR), and thoracoabdominal asynchrony. Inspiratory efforts are dissipated on distorting the chest wall inward rather than recruiting lung volumes. The current study tests the hypothesis that a novel neonatal chest wall suspension splint (SP), designed to provide stability to the compliant chest wall, would reduce inspiratory chest wall retractions and improve lung volumes. Nine preterm infants (29 +/- 1 SE weeks of gestation; 1.59 +/- 0.27 SE kg study weight) were studied at 16 +/- 5 SE days of life at baseline (BL) and following application of the front plate (FP) and the full SP (Hug n Snug Neonatal Chest Splint, Respironics, Inc.). Phase angle of thoracoabdominal motion, CWR, functional residual capacity (FRC), and pulmonary function were evaluated during spontaneous breathing. Compared to BL, there was a significant decrease in anterior CWR (2.21 +/- 0.91 SE vs. 0.25 +/- 0.09 SE mm; P < 0.05), an increase in FRC (16.6 +/- 2.8 SE vs. 27.8 +/- 5.5 SE ml/kg; P < 0.05) and tidal volume (4.8 +/- 1.5 SE vs. 7.3 +/- 1.4 SE ml/kg; P < 0.05), minimal effect on pulmonary compliance (1.98 +/- 0.50 SE vs. 1.72 +/- 0.30 SE ml/cmH2O/kg), and a trend for a decrease in phase angle (128.4 +/- 10.9 SE vs. 111.8 +/- 19.3 SE) with the application of the splint. FRC correlated inversely with severity of CWR across all conditions (P < 0.05, r = -0.68). Phase angle was directly correlated to anterior CWR (r = 0.72; P < 0.05) and correlated inversely with FRC (P < 0.005; r = -0.56). We speculate that by improving CW stability, the use of this splint may reduce the energetic requirements of breathing and, potentially, the need for more invasive ventilatory support in the neonate.

Female↗

Closing volume in normal pregnancy.

Closing volume and other principal lung volumes were measured during and after pregnancy in 10 healthy non-smoking women aged 18--25 yr. There were no significant changes on closing volume or closing capacity. A decrease in functional residual capacity as pregnancy progressed resulted in airway closure during tidal breathing in more than 50% of subjects at term when in a supine position, but this did not occur when they were seated.

Adolescent↗

Twitch pressures in the assessment of diaphragm weakness.

To assess the value of phrenic nerve stimulation in the investigation of diaphragm function, transdiaphragmatic pressures were measured in 20 healthy subjects and in 15 patients with diaphragm weakness, during unilateral and bilateral transcutaneous phrenic nerve stimulation at 1 Hz at functional residual capacity (twitch Pdi). Diaphragm function was initially assessed by measuring transdiaphragmatic pressure during a voluntary manoeuvre, the maximal sniff (sniff Pdi); normal readings were confirmed in the control subjects (102-157 (normal greater than 98) cm H2O in the 10 men, 79-102 (normal greater than 70) cm H2O in the 10 women) and reduced values were found in the 15 patients with diaphragm weakness (7.5-90 cm H2O in the 13 men, 23 and 53 cm H2O in the two women). Twitch Pdi during bilateral phrenic nerve stimulation ranged from 8.8 to 33 cm H2O in the control subjects and from 3.1 to 27 cm H2O in the 10 patients in whom a measurement could be obtained. Bilateral twitch Pdi correlated with sniff Pdi both in the control subjects and in the patients with diaphragm weakness (r = 0.75). Only four patients had a bilateral twitch Pdi below the lowest value seen in the control group, including the three with the lowest sniff Pdi (3.1-8.5 cm H2O). These results indicate that transdiaphragmatic pressure recorded during bilateral phrenic nerve stimulation discriminated between control subjects and patients with known weakness of the diaphragm only when this was severe.

Adult↗

Effects of water immersion on lung volumes: implications for body composition analysis.

Lung volumes of 20 healthy young men were measured before and after water immersion to the neck level. Immersion resulted in significant decreases (P less than 0.01) in forced vital capacity (FVC) (8.9%), expiratory reserve volume (ERV) (61%), total lung capacity (TLC) (5.6%), and functional residual capacity (FRC) (2.9%). Significant increases were observed in inspiratory capacity (IC) (10%) and residual volume (RV) (6.7%). The increase in RV was attributed to a possible "stiffness" of the lung tissue caused by pulmonary vascular engorgement. Densitometric analysis was made on each subject using hydrostatic weighing techniques. Subsequent calculation of body density and per-cent body fat indicated significant (P less than 0.01) differences when using RV measured on land and in water. Body fat was 14.0% using the land RV in the computation of density and decreased to 13.4% using the RV measured in water. It was concluded that when obtaining body density values. RV should be measured concurrently while the subject is in the water.

Adult↗

The effects of intermittent positive pressure breathing on patients with respiratory muscle weakness.

Marked reductions in pulmonary compliance have been noted in patients with respiratory muscle weakness, which greatly contribute to the losses of lung volume. In an attempt to reverse this abnormality and to decrease the work of breathing, we evaluated the effects of a 15-min period of positive pressure, mechanical hyperinflation of the lungs in 10 patients with generalized neuromuscular disorders and long-standing involvement of the respiratory muscles. The vital capacity was 46, and the static expiratory lung compliance was 59% of control values. The recoil pressure of the lung at full inflation was 19 cm H2O. Using positive pressure breathing devices, we inflated the lungs either with inflation pressures ranging between 20 and 40 cm H2O or with volume that were at least twofold larger than the patients' natural inspiratory capacity. Lung volumes, including functional residual capacity, and static pulmonary compliance were not modified by these procedures. Maintaining 10 cm H2O of positive end-expiratory pressure did not alter the results. These findings suggest that (1) alveolar collapse, rather than a simple decrease in the compliance of the surface film of the lung, is the major cause of the low pulmonary compliance in patients with chronic respiratory muscle weakness; (2) these patients do not acutely benefit from intermittent positive breathing treatment.

Adolescent↗

Lung structure and function with age in normal rats and rats with papain emphysema.

Intrapulmonary deposition of the proteolytic enzyme papain produces a lesion resembling emphysema in experimental animals. The natural history of this lesion has not been well defined. The present study was performed to evaluate changes in lung structure and function with aging in normal rats and rats exposed to an aerosol of papain at 2 mo of age. Groups of control and papain-exposed animals were studied at 4, 8, and 18 mo of age. The parameters of lung function studied were specific airways' conductance (G(aw)/TGV), diffusing capacity per unit of alveolar volume (D(Lco)/V(A)), diffusing capacity (D(Lco)), and functional residual capacity (FRC). Morphometric parameters were the postfixation lung volume (V(L)) and mean chord length (L(M)); internal surface area (ISA) and ISA extrapolated to both the mean V(L) of the corresponding papain group and a V(L) of 10 ml (ISA(10)) were calculated. At 4 mo of age L(M) and FRC were significantly increased and ISA, D(Lco)/V(A), and D(Lco) were significantly reduced in the papain group. At 8 mo of age L(M) was significantly increased and ISA was significantly decreased in the papain group: physiologic studies were not performed in this group. At 18 mo of age L(M) was significantly increased and D(Lco)/V(A), D(Lco), and ISA were significantly decreased. Neither progression nor healing of the lesion was observed despite similar lung growth in both groups. This study demonstrates that a single proteolytic lung injury produces a fixed deficit of lung parenchyma. Progressive lung destruction may require repeated or continuous lung injury.

Aerosols↗

Distribution of lung density and mass in patients with emphysema as assessed by quantitative analysis of CT.

STUDY OBJECTIVE: To assess the effects of emphysema on the apex-to-base gradient of lung density (D) and lung mass (M) and to explore the relationship between M and lung function. METHODS: CT scans of whole lungs were performed in 12 healthy subjects and 29 patients who were breathing at functional residual capacity, after which lung function tests were performed. Whole D and M and regional D (RLD) and M (RLM) were calculated. The degree of emphysema was scored. RESULTS: The RLM for each height did not differ significantly between patients with disease and healthy subjects, while RLD was significantly lower in the patients with disease. A less marked nonlinear, increasing, craniocaudal gradient of D was observed in the group with disease, suggesting that the distension increases progressively from the apex to the base. RLD and RLM in the 40 to 90% lung height differed significantly among patients in the emphysema group with normal, high, and low M compared to the healthy subjects. M did not differ significantly between patients with centrilobular and panlobular emphysema, which was thought to stem from the marked variations in the results. Vital capacity was lower in the patients with low M. CONCLUSIONS: The lower RLD in the group with low M was due to both lung overinflation and to tissue loss, while in the groups with high or normal M, it was due only to lung overinflation.

Adult↗

[Bronchodilators reduce air-trapping in COPD patients].

Expiratory flow limitation, air-trapping and hyperinflation are well-known problems in COPD patients. Due to dyspnea during exercise COPD patients often avoid physical activity, which is one of the most important parameters of quality of life. In studies with long-acting bronchodilators, e.g., the anticholinergic agent tiotropiumbromide, a reduction of expiratory flow limitation, hyperinflation and dyspnea could be demonstrated. This was followed by an increase in physical activity. Increase in inspiratory capacity and reduction of functional residual capacity correlated well with the improvement of exercise capacity. In conclusion, bronchodilators such as tiotropiumbromide are able to reduce hyperinflation in COPD patients.

Bronchodilator Agents↗

Effect of lung inhomogeneity on partial flow-volume manoeuvres.

We evaluated the effects of inhomogeneous lung emptying on the relationship of partial to maximal complete expiratory flow by obtaining pre- and post-metaproterenol maximal (MEFV) and partial flow-volume curves in normal subjects and asthmatics. Partial curves were initiated between 65-70% of vital capacity after inspiration from functional residual capacity (PEFV curve) or after deflation from total lung capacity (PEFVDI curve). Since PEFVDI curves were initiated at lower lung volumes than MEFV manoeuvres (but with a similar volume history), non-homogeneous emptying should cause higher flow on PEFVDI than on MEFV manoeuvres. Expiratory flow (Vmax) was highest on MEFV manoeuvres in normals and PEFV curves in asthmatics. Pre- and post-metaproterenol Vmax was very similar on MEFV and PEFVDI manoeuvres in both groups, although Vmax(MEFV) slightly but significantly exceeded Vmax(PEFVDI) in normals and the reverse was true in asthmatics. Lung elastic recoil did not differ significantly on MEFV and PEFVDI manoeuvres in either group. We conclude that asthmatics demonstrate inhomogeneous emptying. However, because flow-volume curves are relatively insensitive to sequences of lung emptying, inhomogeneous emptying during forced expiration only has minor effects on the relationship of partial to maximal expiratory flow.

Adult↗

[Changes in the spirography of paraplegics related to different postures in the air and water].

Respiratory insufficiencies in subjects with spinal cord injury were studied in five situations: in the air (sitting, dorsal supine position, declivous--15 degrees), and immersed in water up to the neck (sitting, dorsal supine position). Results were compared to those for a group of normal subjects. Total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC), vital capacity (VC), forced expiratory volume per second (FEV1) and peak expiratory flow (PEF) were measured and their ratios with theoretical values of each subject were calculated. In handicapped subjects, FEV1 is less significantly diminished than VC and PEF. TLC does not vary, FRC is higher only sitting in the air, RV is more increased. Between situations, FEV1 never varies. In normal subjects, RV does not vary but, sitting in the air, TLC, VC, FRC and PEF increase. In handicapped subjects sitting in the air, VC decreases, RV and FRC increase, TLC and PEF do not vary. In normal and handicapped subjects, the other situations are comparable all together.

Adolescent↗

Value of body plethysmography in preoperative assessment of thoracotomy candidates.

The usefulness of body plethysmography in the assessment of thoracotomy candidates is not well documented. Reported thresholds for operability are generally expressed in absolute values, which do not take into account a patient's size, age or gender. Spirometric and plethysmographic data of 103 patients undergoing thoracotomy were examined for their ability to predict death due to cardiopulmonary insufficiency, pneumonia, and atelectasis during the first 30 postoperative days. Neither plethysmographic nor spirometric parameters could predict atelectasis. Patients who underwent lobectomy were susceptible to the development of atelectasis. A weak correlation between elevated functional residual capacity (FRC) and occurrence of postoperative pneumonia was found. Lung function testing was not able to separate survivors from non-survivors. Patients with pneumonia were at high risk of death in their postoperative course. Because of the non-linear relationship, a correlation coefficient between spirometric and plethysmographic variables was not calculated. The prevalence of cardiac risk factors was high, so the decision for invasive hemodynamic studies should rather be based upon a patient's history than restricted to patients with impaired lung function. Because of methodological differences, and probably insuitable reference values, body plethysmography cannot substitute for spirometry. For FRC and FRC to total lung capacity (FRC/ TLC) ratio, further investigations must be undertaken to establish a correct reference value.

Adult↗

Acute changes of lung volumes and lung mechanics in asthma and in normal subjects.

Lung volumes, pulmonary mechanics, and specific airway conductance (sGaw) were studied before and 15 minutes after 200 microgram of aerosol salbutamol in nine asthmatics undergoing mild spontaneous exacerbations of their disease and in five normal subjects. In addition, three of the normal subjects were studied after voluntarily breathing at high lung volumes for one minute. The normal subjects and four of the asthmatics showed no overall changes in lung volumes or pressure-volume (PV) curves after salbutamol, even though airway dilatation was produced in the asthmatic subjects. In another five asthmatics, salbutamol induced a significant fall in the total lung capacity (TLC) in three, and in the residual volume and functional residual capacity in all five. There was a significant displacement of the PV curve downwards and to the right in all five, with increased lung compliance (Cl stat) in two. The fall in TLC could be accounted for by the increase in lung elasticity. There is reason to believe that this change in lung mechanics could be due to the reversal of asthma-induced stress relaxation. Sustained breathing at high lung volume is known to cause stress relaxation of the lung. However, this breathing pattern did not alter the PV curve or TLC in two of three normal subjects, which is consistent with stress relaxation being rapidly reversible. The other normal subject had an acute shift of the PV curve upwards and to the left after breathing at high lung volume. It has been concluded that stress relaxation is usually rapidly reversed but that in some individuals it may only be slowly reversed. This more persistent form of stress relaxation may contribute to the acute changes of TLC found in some asthmatics.

Adult↗