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PubMed1993

Fibroblast chemotactic response elicited by native bronchoalveolar lavage fluid from patients with fibrosing alveolitis.

BACKGROUND: In fibrosing alveolitis activation of lung fibroblasts is the decisive event in the pathogenetic sequence leading to pulmonary fibrosis. Fibroblast stimulating activity was measured in bronchoalveolar lavage (BAL) fluid to assess its relationship to the activity of fibrosing alveolitis. METHODS: Nine control subjects and 40 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (n = 22) or pulmonary involvement in systemic sclerosis (n = 18) were studied. All patients were followed up by lung function testing for a minimum of six months (mean (SE) 13.3 (1.4) months). Twenty five patients received immunosuppressive therapy and 15 refused. At the beginning of follow up BAL was performed and, as a possible indicator of fibroblast stimulating mediators within the lungs, chemotactic migration of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden-type chambers and expressed as a percentage of the chemoattractant effect of 25 ng/ml platelet derived growth factor. The procollagen III peptide level in BAL fluid served as a marker for collagen synthesis. RESULTS: Chemoattractant activity was elevated in the patients with idiopathic pulmonary fibrosis and systemic sclerosis compared with the control group, (mean (SE) 56.4% (8.5%)) and 72.3% (16.3%) v 12.6% (4.0%). Chemoattractant activity was inversely correlated with total lung capacity (TLC) (r = -0.45) and with vital capacity (VC) (r = -0.33). Procollagen III peptide concentrations in BAL fluid and chemoattractant activity were not significantly correlated. For further evaluation chemoattractant activity of 36% (mean value of controls +2 SD) was used to separate normal (< 36%) from elevated (> or = 36%) activity. At the end of follow up, untreated patients with high chemoattractant activity (> or = 36%) showed a significant reduction of VC, TLC, and exercise arterial oxygen tension (PaO2) and a small decrease in carbon monoxide transfer factor (TLCO), whereas a significant improvement in VC, TLC, and TLCO and a small increase of exercise PaO2 occurred in treated patients with high chemoattractant activity. Patients with low chemoattractant activity (< 36%) showed no consistent change in lung function measurements, irrespective of treatment. In contrast, lung function results and differential cell counts in BAL fluid failed to identify progressive disease. CONCLUSIONS: In patients with fibrosing alveolitis the chemoattractant activity of BAL fluid seems to be an independent indicator of lung fibroblast stimulating activity providing relevant information about disease activity, and may help to improve the clinical management of these patients.

Adult↗
PubMed1984

The effects of minor and moderately severe accidental chest injuries on pulmonary function in man.

Pulmonary function has been measured at intervals after direct chest injuries of mild and moderate severity in 46 patients. Ventilatory capacity (e.g. FEV1) and vital capacity were reduced and the residual volume was increased. Total lung capacity and alveolar volume were also reduced and as a result total pulmonary diffusing capacity (transfer factor) was decreased, however, the remaining lung had a normal diffusion coefficient. Intercostal nerve block at the fracture site did not improve ventilatory capacity although marked pain relief was achieved. Recovery was slower in those patients not admitted to hospital than in the more seriously injured patients who were admitted. It is suggested that more attention should be paid to the outpatient follow-up of such patients, perhaps paying particular attention to physiotherapy.

Accidents↗
PubMed2006

Normal spirometry, gas transfer and lung volume values in Papua, Indonesia.

Spirometry is an efficient and clinically useful tool in the diagnosis and management of chronic lung disease. It relies on an appreciation of normal lung function that can vary between populations. In order to improve the utility of spirometry, gas transfer and lung volume measures for clinical and research use in Papua, Indonesia, we determined lung function in Papuan and non-Papuan Indonesian adults who did not have evidence of lung disease. A cross-sectional survey of Papuan and non-Papuan Indonesians 18 years or older with no history of chronic cough or recent wheeze was made. Spirometry, gas transfer and total lung capacity (TLC) were determined and regression models developed for normal values. The spirometry values were similar but not directly comparable to similar studies in Papua New Guinea populations. Papuan highland residents demonstrated independently greater values of gas transfer and total lung capacity in comparison to lowland Papuans. Values for lung function in apparent respiratory health were shown to differ between Papuan and non-Papuan Indonesian populations and in comparison to reference values derived from non-indonesian populations. Differences in age-related decline in lung function would suggest that simple proportional correction based on values derived from non-Indonesian populations may be inappropriate and would support the development of similar reference values in other populations. Whether differences seen here are innate or occur as a consequence of in-utero and post-partum environmental exposure remains to be accurately elucidated.

Adult↗
PubMed2006

Increased uptake of 111In-octreotide in idiopathic pulmonary fibrosis.

UNLABELLED: Idiopathic pulmonary fibrosis (IPF) is characterized by an uncontrolled accumulation and activation of lung fibroblasts. A modulation of fibroblast activation has been observed in various systems with octreotide, a synthetic somatostatin analog with strong affinity for the somatostatin receptor subtype 2 (sst2). One aim of our study was to evaluate the expression of somatostatin receptors in the lungs of patients with IPF. A second aim was to evaluate the relationship between 111In-octreotide uptake and the effect of pulmonary fibrosis as assessed by lung function tests and parameters and by radiologic findings. METHODS: We investigated 11 patients with IPF, 6 patients with pulmonary fibrosis associated with systemic sclerosis (SSc), and 19 patients with disease not of the lung (control patients). The expression of somatostatin receptors was evaluated in vivo using 111In-octreotide scintigraphy. We evaluated the relationship between 111In-octreotide uptake and the activity of pulmonary fibrosis as assessed by lung function tests, bronchoalveolar lavage (BAL) cellularity, and high-resolution CT (HRCT) of the chest. Planar images and thoracic SPECT (24 h) were performed after injection of 222 MBq of 111In-octreotide. Lung uptake was quantified using the lung-to-background ratio (L/B). In addition, the expression of sst2 was evaluated in vitro, in frozen lung-tissue samples using autoradiography, and in human cultures of lung fibroblasts using a ligand-binding assay. RESULTS: Compared with lung uptake in control patients (median L/B, 1.25; range, 1.14-1.49), lung uptake was increased in all 11 IPF patients (median L/B, 2.63; range, 1.59-3.13; P < 0.001) and in 4 of 6 SSc patients (median L/B, 1.68; range, 1.42-2.16). The L/B was lower in SSc patients than in IPF patients (P = 0.011). Increased uptake correlated with the alteration of lung function (carbon monoxide diffusing capacity [rho = -0.655; P = 0.038], diffusing capacity for carbon monoxide and alveolar volume ratio [rho = -0.627; P = 0.047], vital capacity [rho = -0.609; P = 0.054], and total lung capacity [rho = -0.598; P = 0.058]) and with the intensity of alveolitis (total BAL cellularity [rho = 0.756; P = 0.045], neutrophil counts [rho = 0.738; P = 0.05]), and HRCT fibrosis score (rho = 0.673; P = 0.007). Autoradiography suggested that vascular structures were a prominent binding site. Lung fibroblasts expressed somatostatin receptors in vitro as measured by binding assay. CONCLUSION: Our preliminary results identified an increased expression of sst2 in (mainly idiopathic) pulmonary fibrosis. Lung uptake correlates with the alteration of lung function and with the intensity of alveolitis.

Adult↗
PubMed1975

Cardiac limitation to maximal oxygen transport and changes in components after jogging across the US.

Observations were made before and 3-5 days after prolonged endurance jogging an average of 42 miles/day, 6 days/wk for 2.5 mo by a young male adult who voluntarily initiated a run across the United States. Both arterial PO2 and lactic acid increased. In each instance, the first limitation in circulatory delivery of oxygen was a plateau in stroke volume and cardiac output. Afterward, pulse deficit and systemic arterial pressure fell with exercise and heart rate accelerated. Although there was no change in oxygen transport (Q X CAO2), a reduction in stroke volume was exactly balanced by a rise in arterial oxygen content. Vital capacity, residual volume, and total lung capacity and diffusion capacity for carbon monoxide, hematocrit, and red cell mass increased, while plasma volume diminished and heart size and total blood volume were unchanged.

Adult↗
PubMed1996

Comparison of magnetic and electrical phrenic nerve stimulation in assessment of diaphragmatic contractility.

Unlike the standard electrical approach, cervical magnetic stimulation of the phrenic nerves is less painful and achieves a constant degree of diaphragmatic recruitment, features that should enhance its applicability in a clinical setting. An unexplained phenomenon is the greater transdiaphragmatic twitch pressure (Pditw) with magnetic vs. electrical stimulation. We hypothesized that this greater Pditw is due to coactivation of extradiaphragmatic muscles. Because impedance to rib cage expansion is increased at high lung volumes and efficiency of extradiaphragmatic muscles is less than that of the diaphragm, we reasoned that the difference between electrical Pditw and magnetic Pditw would be less evident at high volumes than at end-expiratory lung volume. In human volunteers, magnetic Pditw and electrical Pditw were 37.7 +/- 1.9 (SE) and 32.3 +/- 2.2 cmH2O, respectively, at end-expiratory lung volume (P < 0.005) and 24.0 +/- 2.9 and 27.2 +/- 2.8 cmH2O, respectively, at one-half inspiratory capacity (not significant); at total lung capacity, magnetic Pditw was less than electrical Pditw (10.6 +/- 0.8 and 16.2 +/- 2.9 cmH2O, respectively; P < 0.05). Magnetic stimulation caused significant extradiaphragmatic muscle depolarization and rib cage expansion, whereas electrical stimulation caused virtually no extradiaphragmatic muscle depolarization and rib cage deflation. Despite these differences, the induction of respiratory muscle fatigue produced reductions in both electrical and magnetic Pditw values (P < 0.01), which were of similar magnitude and closely correlated (r = 0.96). In conclusion, magnetic stimulation recruits both extradiaphragmatic and diaphragmatic muscles, and it is equally as effective as electrical stimulation in detecting diaphragmatic fatigue.

Adult↗
PubMed2001

The role of domiciliary nebulizers in managing patients with severe COPD.

The difficulty of assessing nebulizer responses in chronic obstructive pulmonary disease (COPD) has been demonstrated before. This study aims to re-examine both the role of domiciliary nebulizers in COPD and also bronchodilator (BD) assessment in individuals. In a double-blind, randomized, cross-over trial, 19 stable patients with severe COPD were given the following medication 6-hourly for 2-week periods: (1) nebulized salbutamol 2.5 mg with ipratropium 0.5 mg and placebo inhalers (MDI) with spacer; (2) placebo nebules and inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer; (3) inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer (but no placebo nebulized drugs). Both nebulized and MDI drugs produced highly significant improvements in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), specific airways conductance, 6-min walking distance (6MWD) and residual volume. There were no significant differences between BD responses obtained after active nebulized and active MDI BDs. From the diary cards, 2 weeks of active nebulized BDs produced a slightly higher median peak expiratory flow (PEF) than active MDI BDs (236 and 219 l m(-1), respectively, P=0.01) and slightly less extra inhaler use (0.8 and 1.1 puffs, respectively, P<0.05) but no significant difference in dyspnoea or quality of life (QOL) scores. There were significant correlations between domiciliary PEF and acute BD-induced changes in FVC and 6MWD, and also between domiciliary dyspnoea scores and acute changes in both total lung capacity and 6MWD. In conclusion, nebulized medication conferred little clinical advantage over the regular use of inhalers with spacers in this group of patients with severe COPD. However, acute changes in total lung capacity, FVC and 6MWD may be useful predictors of the longer-term effects of nebulized BDs in individual patients.

Administration, Inhalation↗
PubMed1986

Computed tomography based estimates of regional gas and tissue volume of the lung in supine subjects with chronic airflow limitation or fibrosing alveolitis.

Twelve patients with chronic airflow limitation and 12 patients with a histological diagnosis of fibrosing alveolitis were studied. The calculated mean (SD) tissue volume of a single lung at total lung capacity was 467 (91) ml in the patients with alveolitis, which was 43% (14%) more than predicted for healthy people of the same age, sex, and height. The tissue volume of a single lung at total lung capacity was 436 (82) ml in the patients with chronic airflow limitation, which was 26% (21%) more than predicted. At residual volumes the tissue contents of the fibrotic and the obstructed lungs changed very little (to 407 (84) ml and 433 (84) ml respectively). This allowed tissue volume to be used as a marker of position within the lung, to match inspiratory and expiratory slices and to calculate regional ventilation. In both groups local ventilation was diminished and more variable than in healthy lungs--that is, in the mid 70% of lung volume the local residual volume to total gas volume ratios (RV/TGV) were 32% (10%) in the fibrotic group and 66% (14%) in the group with chronic airflow limitation, compared with 23% (5%) in healthy subjects. As expected, the fibrotic lungs were much denser (0.246 (0.036) g/ml) and the lungs with chronic airflow obstruction were less dense (0.114 (0.026) g/ml) than were healthy lungs (0.126 (0.017) g/ml).

Adult↗
PubMed2000

Pulmonary lymphangioleiomyomatosis: correlation of ventilation-perfusion scintigraphy, chest radiography, and CT with pulmonary function tests.

PURPOSE: To determine the findings on ventilation-perfusion (V-P) scintigrams, computed tomographic (CT) scans, and chest radiographs and correlate them with pulmonary function test results in patients with lymphangioleiomyomatosis. MATERIALS AND METHODS: V-P scintigraphy, chest radiography, conventional and thin-section CT, and pulmonary function tests were performed in 39 patients. The images were graded on a scale of 0 (normal) to 3 (severely abnormal). RESULTS: Imaging abnormalities were found on 92% of ventilation scintigrams, 92% of perfusion scintigrams, 79% of chest radiographs, 100% of CT scans, and 100% of thin-section CT scans. On ventilation scintigrams, 28 (72%) patients demonstrated a speckling pattern. On CT scans, all patients had pulmonary cysts. Univariate analysis showed that extent of disease on chest radiographs and CT scans, cyst size, V-P abnormalities, and degree of speckling were inversely correlated with forced expiratory volume in one second (FEV(1)), diffusing capacity of lung for carbon monoxide, and the ratio of FEV(1) to forced vital capacity (FVC) (P <.01) but not with FVC and total lung capacity. Larger cyst size correlated with extent of disease at CT, but not significantly (P =.056). CONCLUSION: Scintigraphic and radiologic abnormalities are seen in a majority of patients with lymphangioleiomyomatosis. On ventilation scintigrams, a frequently seen speckling pattern may be related to accumulation of radionuclide in pulmonary cysts-a hallmark of the disease at CT. Findings with each imaging modality correlate with certain pulmonary functions.

Adult↗
PubMed1986

Ventilation-perfusion relationships in interstitial lung disease.

Ten patients with interstitial lung disease were studied with regard to pulmonary gas exchange and diffusion limit at rest and during exercise. The total lung capacity was reduced to 64% and the transfer factor of the lung to 36% of reference. Pulmonary vascular resistance was increased by 50% above the upper normal limit. The ventilation-perfusion relationship (VA/Q), assessed by a multiple inert gas elimination technique, showed 2% shunt and 5% of lung blood flow perfusing regions with a low VA/Q (VA/Q less than 0.1) at rest. PaO2 derived from the VA/Q distribution was 9.3 kPa and correlated significantly (p less than 0.01) with measured PaO2 (9.9 kPa). During light exercise (30 W), the sum of the shunt and perfusion of low VA/Q regions was unaltered (7%), and PaO2 derived from the VA/Q distribution was the same as at rest (9.0 kPa). Measured PaO2 fell, however, to 7.1 kPa and the alveolar-oxygen tension difference (P(A-a)O2) was doubled to 7.0 kPa. It is concluded that a limitation on diffusion across the alveolar-capillary membrane developed during exercise, contributing approximately 30% to P(A-a)O2.

Adult↗
PubMedDate not supplied

Nonuniformity of diffusing capacity from small alveolar gas samples is increased in smokers.

BACKGROUND: Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSM manoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer. OBJECTIVE: To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLcoSB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity. PARTICIPANTS AND DESIGN: Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates. METHODS: Both smokers and nonsmokers performed SBWSM manoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB-3EQ was calculated from the total alveolar gas sample. DLcoSB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB-3EQ from the entire alveolar gas sample. An index of variation (DI) among the small-sample DLcoSB-3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix). RESULTS: For SBWSM, DI was increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and Sn. The decrease in DI with breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVC manoeuvres, there were no differences due to smoking in Sn or Emix, but DI was increased in smokers and correlated with age and smoking pack-years, but not with Sn. CONCLUSIONS: For SBWSM manoeuvres the increase in DI in smokers correlated with breath hold time-dependent increases in Sn, suggesting that the changes in DI reflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVC manoeuvres, the increase in DI in smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DI during this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.

Adult↗
PubMed2000

Evaluation of diffusing capacity in patients with a restrictive lung disease.

BACKGROUND: In healthy volunteers, the single-breath diffusing capacity of the lung for carbon monoxide (DLCO) decreases and DLCO normalized per liter alveolar volume (VA; DLCO/VA) increases if VA is decreased. We hypothesized that comparison of DLCO/VA with its predicted value at predicted total lung capacity (TLC) will result in an underestimation of the diffusion disorder in patients with a restrictive lung disease, if a similar relationship exists between DLCO/VA and lung volume as found in healthy volunteers. OBJECTIVE: To test this hypothesis, we studied total gas transfer DLCO and DLCO/VA as functions of VA in patients who developed a restrictive lung disease and a diffusion disorder in a short period of time. DESIGN: An observational survey. SETTING: Pulmonary function department. PATIENTS: Thirteen patients without any initial pulmonary pathology who developed the mentioned pulmonary pathology due to bleomycin treatment. INTERVENTIONS: Bleomycin treatment. MEASUREMENTS AND RESULTS: We performed the single-breath test at various VA levels before, during, and after bleomycin treatment. In the majority of the patients, the DLCO vs VA relationship remained parabolic, but shifted downwards during therapy. Therefore, the linear DLCO/VA vs VA relationship shifted downwards, while the negative slope was not changed, indicating the development of a decreased gas transfer. Six patients also developed a volume restriction. CONCLUSIONS: The agreement of the data with the hypothesis increased its probability. Consequently, to evaluate a diffusion disorder, DLCO/VA at a lower actual TLC of patients with a lung restriction should be compared to a reference DLCO/VA at a lung volume equal to the actual TLC.

Adult↗
PubMedDate not supplied

The pathophysiology of tension pneumothorax in ventilated swine.

It remains unclear as to whether the cardiovascular collapse observed in tension pneumothorax (TP) is strictly a mechanical pressure-related phenomenon or secondary to hypoxemia. This study describes the pathophysiologic changes associated with a surgically induced progressive TP in a ventilated swine model. With a balloon occlusion catheter surgically placed into the pleural space, progressive volumes of pneumothorax were created in six anesthetized pigs on positive-pressure ventilation. Air was introduced into the right hemithorax in 100-mL increments every 4-5 min, with measurements of heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), mean intrapleural pressure (MIP), oxygen saturation (O2%), arterial blood gas (ABG), and cardiac output (C.O.). With the induced progressive TP, results showed that O2% measures decreased immediately and continued to decline throughout the experiment to levels below 50% prior to cardiovascular collapse. The MAP and HR remained relatively stable until approximately 57% total lung capacity progressive TP (600 mL) was reached. At this point, a significant decline in MAP and increase in HR was noted, indicating tension physiology. The C.O. showed a small but significant decrease after 200 mL of air was injected, with a progressive decline after this point. At > 97% total lung capacity TP, lethal cardiovascular collapse occurred in all animals and was associated with an abrupt drop in C.O., HR, and MAP. There was a concurrent equalization of MIP with CVP at the point of collapse. Arterial blood gas measures correlated with O2% trends during the trials. We conclude that the findings of this study support the alternative hypothesis that significant hypoxemia occurs early and precedes hypotension in ventilated animals with TP. Occlusive mechanical compression, suggested by equalization of MIP and CVP, is probably a late event.

Analysis of Variance↗
PubMed1985

Rib cage mobility in pectus excavatum.

Pectus excavatum is generally regarded as a cosmetic deformity; however, some children with pectus excavatum complain of chest pain and exercise limitation. Physiologic studies sometimes show mild restrictive changes and suggest an increased oxygen cost of breathing. Limitation of rib cage mobility related to the deformity may explain these findings. If rib cage mobility is limited, the ability of the actively inspiring rib cage to lower abdominal pressure would be decreased. If this were so, increased swings in abdominal pressure would be seen during the respiratory cycle, especially at times of stress such as during exercise. To test the hypothesis that pectus excavatum is associated with decreased rib cage mobility, we studied 11 patients with pectus excavatum and 11 control subjects. Four control subjects were also studied with rib cage mobility restricted by chest wall strapping sufficient to decrease vital capacity by 5, 10, and 40%. Gastric pressure was measured using balloon catheters and was used as an index of abdominal pressure. Flow at the mouth was recorded and integrated to give volume. Measurements were made at rest, immediately after exercise, and during graded voluntary inspiration to total lung capacity. Gastric pressure was related to tidal volume, and pressure-volume loops were constructed. There were no differences in abdominal pressure swings during respiration between the patients with pectus excavatum and the control subjects. Both groups showed moderate increase in gastric pressure during inspiration at rest and smaller increases or even decreases in abdominal pressure at end inspiration after exercise and at total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2003

Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis.

There is significant heterogeneity in survival time among patients with idiopathic pulmonary fibrosis. Studies of baseline clinical and physiologic variables as predictors of survival time have reported inconsistent results. We evaluated the predictive value of changes in clinical and physiologic variables over time for survival time in 81 patients with biopsy-proven idiopathic pulmonary fibrosis. Six-month changes in dyspnea score, total lung capacity, thoracic gas volume, FVC, FEV1, diffusing capacity of carbon monoxide, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time even after adjustment for baseline values. Analyses were repeated on 51 patients with 12-month change data. Twelve-month changes in dyspnea score, total lung capacity, FVC, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time after adjustment for baseline values. Evaluation of changes in clinical and physiological variables over 6 and 12 months may provide clinicians with more accurate prognostic information than baseline values alone.

Aged↗
PubMed2006

Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial.

In chronic obstructive pulmonary disease (COPD), the sympathetic nervous system, as well as the renin-angiotensin system, is activated with possible negative systemic effects on skeletal muscles. Angiotensin II type-1 receptor blockers inhibit the sympathetic and renin-angiotensin systems and might improve skeletal and respiratory muscle strength in patients in whom these systems are activated. The effects of the angiotensin receptor blocker irbesartan given over 4 months was evaluated in 60 patients with COPD and a forced expiratory volume in one second of <50% of the predicted value and without obvious cardiovascular disease that would necessitate the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Irbesartan was well tolerated, but did not exert a significant effect on the primary end-point maximum inspiratory pressure. Spirometric results were not affected, but total lung capacity was reduced. Irbesartan led to a significant decrease in haematocrit (46.4+/-3.6 to 43.9+/-4.3% versus 47.5+/-2.4 to 48.7+/-3.0% with placebo). In conclusion, respiratory muscle strength in chronic obstructive pulmonary disease patients was not influenced by angiotensin II receptor blockade. However, the changes in haematocrit and total lung capacity following irbesartan raise the possibility that well-known cardiovascular drugs can produce unanticipated beneficial effects in chronic obstructive pulmonary disease patients.

Angiotensin II Type 1 Receptor Blockers↗
PubMed1994

Lung volumes and expiratory flow limitation during exercise in interstitial lung disease.

Lung volumes were measured at rest and during exercise by an open-circuit N2-washout technique in patients with interstitial lung disease (ILD). Exercise tidal flow-volume (F-V) curves were also compared with maximal F-V curves to investigate whether these patients demonstrated flow limitation. Seven patients underwent 4 min of constant work rate bicycle ergometer exercise at 40, 70, and 90% of their previously determined maximal work rates. End-expiratory lung volume and total lung capacity were measured at rest and near the end of each period of exercise. There was no significant change in end-expiratory lung volume or total lung capacity when resting measurements were compared with measurements at 40, 70, and 90% work rates. During exercise, expiratory flow limitation was evident in four patients who reported stopping exercise because of dyspnea. In the remaining patients who discontinued exercise because of leg fatigue, no flow limitation was evident. In all patients, the mean ratio of maximal minute ventilation to maximal ventilatory capacity (calculated from maximal F-V curves) was 67%. We conclude that lung volumes during exercise do not significantly differ from those at rest in this population and that patients with ILD may demonstrate expiratory flow limitation during exercise. Furthermore, because most patients with ILD are not breathing near their maximal ventilatory capacity at the end of exercise, we suggest that respiratory mechanics are not the primary cause of their exercise limitation.

Airway Obstruction↗
PubMed1979

Diffusing capacity at different lung volumes during breath holding and rebreathing.

Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) increases as lung volume increases above functional residual capacity (FRC). However, the physiological mechanism responsible for this increase remains controversial. This volume dependence of diffusing capacity could reflect changing regional distribution of inspired air as lung volume increases rather than a change in capillary blood volume or surface area for gas exchange. We measured DLCO during breath holding and during rebreathing with a technique employed to mix respired gases throughout the lung thereby minimizing regional distribution differences. Measurements were made 1,500 ml above FRC and near total lung capacity (TLC). Breath holding DLCO was 18% higher near TLC than at 1,500 ml above FRC (P less than 0.05). Rebreathing DLCO was 16% higher near TCL than at 1,500 ml above FRC (P less than 0.01). Equality of results by the two techniques indicates that changes in DLCO with lung volume are not a consequence of the changing distribution of inspired air. Our results are compatible with the hypothesis that effective surface area of the lung increases as lung volume expands.

Adult↗