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PubMed1995

The effects of antireflux therapy on pulmonary function in patients with severe gastroesophageal reflux disease. Department of Veterans Affairs Gastroesophageal Reflux Disease Study Group.

OBJECTIVES: Gastroesophageal reflux can induce bronchospasm, and antireflux therapy has been shown to improve pulmonary function in patients who have gastroesophageal reflux disease (GERD) associated with asthma. Our objective was to study the pulmonary effects of antireflux therapy in patients who had severe GERD without clinically apparent lung disease. METHODS: In a Department of Veterans Affairs Cooperative Study, patients who had complicated GERD without important lung disease were randomly assigned to receive one of three types of antireflux treatment, including two kinds of medical therapy and a surgical therapy. Patients had pulmonary function tests (PFTs), including total lung capacity, residual volume, forced vital capacity, forced expiratory volume in 1 s, maximal midexpiratory flow, and diffusing capacity for carbon monoxide. RESULTS: Two hundred forty-seven patients (243 men, four women; mean age 58 yr) entered the randomized trial, and 151 returned for PFTs at 1 yr. For the entire study group and for all three treatment groups, mean values for PFTs at 1 yr did not differ significantly from those at baseline. Even in subgroups of patients whose baseline PFTs were abnormal and whose esophagitis had healed completely, there were no significant changes in results of PFTs. CONCLUSIONS: For veteran patients with severe GERD and no obvious lung disease, 1 yr of antireflux therapy had no important effect on pulmonary function. These findings suggest that GERD is not commonly associated with inapparent, reversible pulmonary dysfunction.

Female↗
PubMed1997

Inspiratory maneuver effects on peak expiratory flow. Role of lung elastic recoil and expiratory pressure.

We investigated the effects of two different inspiratory maneuvers (fast or slow) on the ability of normal subjects to generate peak expiratory flows (PEF) and maximal dynamic expiratory pressures (Pexp) during the performance of a forced vital capacity maneuver. During the fast maneuver (F), the subject inspired rapidly to total lung capacity (TLC) and immediately performed a maximal expiration, whereas in the slow maneuver (S) the subject inspired slowly to TLC, paused for 4-5 s at TLC and then performed a maximal expiration. Ten normal subjects performed a series of such maneuvers. In addition to PEF and Pexp, we measured EMG activity of abdominal (EMGabd) and rib cage muscles, and lung elastic recoil pressure (PesL). Overall, F yielded higher PEF values than S (by approximately 7%); in addition, PesL, Pexp, rate of rise of Pexp (dPexp/dt), and EMGabd were similarly higher with F than with S (p < 0.05 for all). Analysis of individual data showed that the intermaneuver differences in PEF were largely explained by differences in PesL, Pexp or dPexp/dt. Our data suggest that, in comparison with the slow maneuver, the fast maneuver induces a greater change in both the lung elastic recoil and expiratory muscle activation which account for differences in PEF between the two maneuvers. The enhanced expiratory muscle activation with the fast maneuver suggests a specific inspiratory-expiratory muscle interaction analogous to agonist-antagonist interactions described for skeletal muscles.

Adult↗
PubMed2005

Genomewide linkage analysis identifies novel genetic Loci for lung function in mice.

RATIONALE: Pulmonary function, including lung volumes and compliance, may be genetically determined, but few genetic polymorphisms have been identified that control these traits. We used an experimental approach and performed the first whole genome scan for pulmonary function in mice. OBJECTIVES AND METHODS: To identify novel chromosomal regions contributing to lung function, quantitative trait locus linkage analysis was applied in N(2) backcross and F(2) intercross mice derived from two inbred strains-C3H/HeJ and JF1/Msf-with extremely divergent phenotypes. MAIN RESULTS: Significant linkages to total lung capacity with LOD (logarithm of the odds) scores up to 6.0 were detected on chromosomes 15 and 17, to dead space volume and lung compliance on chromosomes 5 and 15 (LOD scores higher than 4.0), to lung compliance also on chromosome 19 (LOD score of 5.8), and to diffusing capacity on chromosomes 15 and 17 (LOD scores up to 5.0). The region of interest on chromosome 17 near D17Mit133 contains a syntenic region to human chromosome 6q27, which was recently identified to be linked to lung function in humans. The identified intervals harbor valuable candidate genes, such as the relaxin1 and transforming growth factor beta receptor 3 gene, which revealed missense polymorphisms between the parental strains. CONCLUSION: The study provides evidence for linkage of different measures of lung function on murine chromosomes 5, 15, 17, and 19 and suggests novel candidate genes that may also affect the expression of human pulmonary function.

Animals↗
PubMed1995

A finite element analysis of the effects of the abdomen on regional lung expansion.

A finite element model of the dog lung, heart and abdomen, consisting of three solid linearly elastic bodies, was developed to study the effects of gravity on the vertical stress distribution and lung volume in different body positions at functional residual capacity (FRC). The geometry of the lung was obtained from an isolated dried dog lung after inflation to total lung capacity (TLC). The compliance of the rib cage, diaphragm and the abdomen was simulated by spring elements located on their surfaces. In the prone position, gravitational forces acting only on the lung contributed to the vertical gradient (0.19 cmH2O/cm) in transpulmonary pressure (Ptp). This result was independent of chest wall compliance. In the supine position, the addition of the heart and abdomen with a compliant diaphragm and abdominal walls increased the vertical Ptp gradient to 0.53 cmH2O/cm. In the head-up (upright) position, both heart and abdominal weight contributed to the vertical gradient (0.47 cmH2O/cm). Diaphragmatic compliance was of less importance to the vertical gradient in the head-up and head-down positions in the absence of the abdomen. The smallest vertical gradient (0.11 cmH2O/cm) was obtained in the head-down position with abdominal weight reducing the gradient caused by lung weight. Lung volume at FRC was virtually unaffected by gravity in the prone body position, was reduced by gravity in the supine and head-down positions but increased in the head-up position. The effects of a compliant diaphragm and abdominal weight are important contributors to the distribution of stress and volume in the intact lung.

Abdomen↗
PubMed1983

[New elements in the interpretation of flow-volume curves].

We have measured flow-volume curves (FV) in 167 normal individuals of both sexes aged 20 to 89. All were non-smokers and none had cardio-respiratory disease. The flows at 25, 50 and 75 per cent of vital capacity (VC) as well as flows normalized by VC or total lung capacity (TLC) gave, in general, good correlation coefficients with age. The parameters V25/TLC and especially V50/TLC gave for the best correlations with age and we suggest these parameters in future when flow volume curves are used to assess respiratory pathophysiology. Normal values as well as regression equations of these parameters with age are proposed for various age groups in the 20-89 years age range.

Adult↗
PubMed1992

Accelerated loss of lung function and alveolitis in a longitudinal study of non-smoking individuals with occupational exposure to asbestos.

Long-term asbestos workers who insulate pipes and boilers may develop interstitial lung disease associated with loss of lung function. To quantitate annual loss of lung function, 77 individuals with chest X-rays greater than or equal to 1/0 ILO category who were life-long non-smokers or ex-smokers for greater than 5 years were evaluated. Study parameters included pulmonary function tests and bronchoalveolar lavage for a mean of 3 visits over 30 +/- 2 months. The study participants were 56 +/- 1 years old and had 31 +/- 1 years' occupational exposure to asbestos. At the first visit, multiple regression analysis revealed significant associations between rales or radiographic opacities and VC, FEV1, and total lung capacity; significant associations were also found between neutrophils/ml lavage fluid with FEV1 and diffusing capacity (all p less than 0.05). Annual declines for the asbestos-exposed were VC -92 +/- 28 ml/yr and FEV1 -66 +/- 21 ml/yr. Declines in VC and FEV1 were less in those with reduced lung function at the initial visit. There were no significant associations between any of the annual declines and cells recovered by bronchoalveolar lavage. Compared to other asbestos-exposed cohorts followed longitudinally, asbestos insulators with radiographs greater than or equal to 1/0 and exposure greater than or equal to 20 years have larger rates of FVC and FEV1 decline for both non-smokers and ex-smokers.

Asbestos↗
PubMed1998

Association of pulmonary function testing abnormalities and severe veno-occlusive disease of the liver after marrow transplantation.

We investigated an association between pulmonary function testing (PFT) before bone marrow transplantation and the development of severe veno-occlusive disease (VOD) of the liver. We previously noted that reductions in diffusing capacity of the lung for carbon monoxide (corrected for hemoglobin) (D(L)COc) were associated with mortality after transplantation, but this was not caused by respiratory failure. We performed a case-series review of prospectively collected data from 307 marrow recipients who underwent PFT within 2 weeks of transplantation. Of these, 170 (56%) developed VOD; 39 (13%) mild, 81 (26%) moderate, and 50 (16%) severe or fatal. Both total lung capacity (TLC) and D(L)COc were associated with severe VOD in univariate analysis (P = 0.006 for each). However, D(L)COc entered logistic regression models that contained variables for all known risk factors for severe VOD, while TLC did not contribute additional predictive information. The odds ratio (OR) associated with a D(L)COc below the lower limits of normal (70% of predicted) was 2.4 (95 % CI, 1.0 to 5.4; P = 0.04). We conclude that reduced diffusion capacity of the lung measured before marrow transplantation is an independent risk for severe hepatic VOD. We speculate that the decreased D(l)COc indicates pre-existing systemic endothelial cell damage and a susceptibility to severe hepatic injury from chemotherapy.

Adolescent↗
PubMed1983

Effects of prenatal nitrofen exposure on postnatal lung function in the rat.

The herbicide Nitrofen was administered by gavage to pregnant F-344 rats during Days 10 through 13 of gestation. Postnatal lung function was measured in male progeny at 3 and 6 weeks of age. There were no differences in body weight or wet and dry lung weights between control and Nitrofen-exposed rats in either age group. Nitrofen produced no observable effects on lung function at 3 weeks of age. However, by 6 weeks of age the Nitrofen-exposed animals had significant decreases in tidal volume (p less than 0.01), vital capacity (p less than 0.01), total lung capacity (p less than 0.05), and quasi-static lung compliance (p less than 0.01). There was also a mild ventilation inhomogeneity, as indicated by significant increases in the nitrogen washout slope (p less than 0.01) and the moment ratio (p less than 0.05). Histopathology of lung, liver, kidney, and testes was not significantly altered by Nitrofen exposure. These data suggest that prenatal Nitrofen exposure may have an effect on postnatal lung maturation in the rat and could potentially be useful as a model of pulmonary hypoplasia.

Aging↗
PubMed1989

Total respiratory resistance and reactance in patients with diffuse interstitial lung disease.

In 54 patients with interstitial lung diseases and no signs of airway obstruction we measured lung volumes, maximal expiratory flows, diffusing capacity (DLCO), total respiratory resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz by means of the forced oscillation technique. In all patients DLCO was less than 75% of the expected value. Patients were classified into two groups depending on total lung capacity (TLC): group A with TLC less than 80% of expected, and group B with TLC of 80% or more. Group A demonstrated a decrease of Xrs especially at low frequencies, with small, not significant changes in Rrs. In the patients in this group with the lowest values of TLC (less than 50%), we observed an increase of Rrs at low frequencies causing a negative frequency dependence of Rrs. In group B no distinct changes of Rrs and Xrs occurred. Canonical correlation analysis between routine lung function data and forced oscillation parameters, showed tight correlations between TLC in absolute value or VC in percent of the predicted value on the one hand and average level of Xrs and average slope of Xrs (and Rrs) vs frequency curves on the other hand. Measurements of lung mechanics in five additional patients and comparison with a model of the respiratory system suggest that the changes of Rrs and Xrs are not explained totally by the observed increase in lung tissue resistance and decrease in lung compliance. The observed changes in Rrs and Xrs are not specific for restrictive lung disorders; similar changes are met also in moderately advanced obstructive diseases.

Adult↗
PubMed2002

Normative values of pulmonary function testing in Chinese adults.

OBJECTIVES: To compare the difference in pulmonary function between Caucasians and Chinese and assess the best reference values of pulmonary function for Chinese adults. METHODS: Values for pulmonary function were predicted by tests on 4773 Chinese healthy subjects (male: 2560, female: 2213, aged 15-78 years) in six parts (north, northeast, northwest, east, southwest and south) of China. Prediction equations of the European Community for Steel and Coal (ECSC), other equations for overseas Chinese or for Caucasians were also selected. The regression coefficients of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, total lung capacity (TLC) and residual volume (RV) were summarized. RESULTS: ECSC predictions were closer to the Chinese ones than other selected equations. Comparison with ECSC predictions showed that on average the values for FVC, FEV1 were 5.3% smaller in Chinese males and 3.3% smaller in Chinese females, with the maximal differences in south China and the minimal differences in North China. RV and TLC in Chinese were lower than in Caucasians (males 4.8%, 5.5%, respectively; females 8.7% and 6.0%, respectively). Conversion factors were given for adjusting ECSC equations to fit Chinese. CONCLUSIONS: For predicting values of pulmonary function in Chinese, we suggest to use the equations reported here. Alternatively, ECSC regression equations may be used with appropriate conversion factors.

Adolescent↗
PubMed2001

Evaluation of bronchodilator responses in patients with "irreversible" emphysema.

Given the emerging physiological and clinical rationale for pharmacological lung-volume reduction, assessment of volume responses to bronchodilators is likely to be highly relevant in chronic obstructive pulmonary disease (COPD). The authors examined the magnitude of lung-volume reduction after acute bronchodilator treatment in patients with advanced emphysema. Eighty-four stable patients with emphysema (mean+/-SEM forced expiratory volume in one second (FEV1): 32+/-1% predicted) performed spirometry and body plethysmography before and 15-30 min after 200 microg salbutamol. Only irreversible patients with a postbronchodilator change in FEV1 <10% pred were considered in this study. Postsalbutamol, the majority of subjects (83%) had significant improvements in one or more lung volumes: on average, residual volume (RV), functional residual capacity (FRC), inspiratory capacity (IC), forced vital capacity and slow vital capacity changed by -18+/-2, -10+/-1, 8+/-1, 9+/-1 and 7+/-1% pred (p<0.0005 each). Total lung capacity (TLC) decreased 0.12+/-0.04 L (p<0.01). Change in IC reflected change in FRC (r=-0.60, p<0.0005), but more strongly in the 57% of patients with no significant change in TLC (r=-0.93, p<0.0005). The magnitude and frequency of volume responses were greatest in patients with the most severe COPD; for example, RV decreased by 0.51+/-0.09 L (23+/-4% pred) and 0.27+/-0.04 L (14+/-2% pred) in severe and moderate subgroups, respectively. Significant reductions in lung hyperinflation occurred in the absence of a change in forced expiratory volume in one second after low-dose salbutamol in a majority of patients with advanced emphysema; the greatest changes occurred in those with the most severe disease.

Aged↗
PubMed1985

Changes in lung volume and deflation stability in hyaline membrane disease.

Total lung capacity (TLC), inspiratory capacity, functional residual capacity, and deflation stability of prematurely delivered Macaca nemestrina primates were measured serially during development of, and recovery from, hyaline membrane disease (HMD) to relate changes in lung volumes to changes in deflation stability. Gestational age-matched primates that did not develop HMD served as controls. TLC, measured by N2 washout, fell at 2-12 h of age (P less than 0.0001) in animals with HMD and remained lower than controls for at least 48 h (P less than 0.005). However, deflation stability, defined as the fraction of TLC remaining upon deflation to 10 cm H2O, improved from 2 to 12 h of age (P less than 0.001). Postmortem studies confirm the measurements of TLC and deflation stability and provide evidence that interstitial thickening and obstruction of air spaces with debris may be partially responsible for the observed changes in TLC in primates that develop HMD. It has been assumed that TLC is reduced in HMD because of atelectasis from elevated alveolar surface tension, but the sequential measurements in these animals suggest that other mechanisms also contribute.

Animals↗
PubMed1982

Pulmonary functions during peritoneal dialysis.

Lung volumes, flows, flow volume loop, diffusing capacity and closing volume were studied in 7 patients (Group I) before, with 2 liter dialyzate in the peritoneal cavity and after 8 hours of peritoneal dialysis. The functional residual capacity, residual volume and the total lung capacity decreased (P less than 0.01, less than 0.05, and less than 0.05 respectively) with 2 liter dialyzate in the peritoneal cavity and returned to baseline after the dialyzate was removed. Arterial blood gas analysis was performed in another 8 patients (Group II) before, with 2 liter dialyzate in the peritoneal cavity, and after the dialyzate had been drained. No significant difference was observed in PaO2, PaCO2 or pHa during any phase of the study. It is concluded that except for a minor decrease in FRC, RV and TLC, there were no deleterious effects with the use of 2 liter dialyzate volume on gas exchange or pulmonary functions during peritoneal dialysis.

Adult↗
PubMed1977

Diaphragm function and lung involvement in systemic lupus erythematosus.

Lung involvement was assessed in 30 consecutive patients with systemic lupus erythematosus (SLE), not selected by respiratory symptoms. Pulmonary function tests revealed a higher rate of abnormality than either clinical history or radiography. The single breath carbon monoxide diffusing capacity was below 80 per cent of the predicted value in 24 patients (80 per cent), and a reduced total lung capacity was present in 13 (43 per cent). There was a weak correlation between the severity of the functional defect and disease activity, assessed antinuclear factor and DNA binding. No correlation was found with serum complement of Clq precipitation. Since pulmonary fibrosis in SLE is uncommon it cannot account for the high frequency of abnormal findings, and the pathogenesis of the functional changes is probably multifactorial. In seven of the patients with the smallest lung volumes, measurements of static pressure volume curves and of maximum respiratory pressures indicated extrapulmonary volume restriction. In five of these patients, diaphragm function was specifically assessed and found to be grossly abnormal in four. The inability of the diaphragm to generate normal pressure may be due to either severe weakness or immobility following extensive pleural adhesions. The well recognized syndrome of "shrinking lungs" and high "sluggish" diaphragms with clear lung fields on radiography is probably due to dysfunction of the diaphragm rather than to primary intrapulmonary pathology.

Adolescent↗
PubMed1990

Tracheal smooth muscle mechanics in vivo.

We applied the technique of sonomicrometry to directly measure length changes of the trachealis muscle in vivo. Pairs of small 1-mm piezoelectric transducers were placed in parallel with the muscle fibers in the posterior tracheal wall in seven anesthetized dogs. Length changes were recorded during mechanical ventilation and during complete pressure-volume curves of the lung. The trachealis muscle showed spontaneous fluctuations in base-line length that disappeared after vagotomy. Before vagotomy passive pressure-length curves showed marked hysteresis and length changed by 18.5 +/- 13.2% (SD) resting length at functional residual capacity (LFRC) from FRC to total lung capacity (TLC) and by 28.2 +/- 16.2% LFRC from FRC to residual volume (RV). After vagotomy hysteresis decreased considerably and length now changed by 10.4 +/- 3.7% LFRC from FRC to TLC and by 32.5 +/- 14.6% LFRC from FRC to RV. Bilateral supramaximal vagal stimulation produced a mean maximal active shortening of 28.8 +/- 14.2% resting length at any lung volume (LR) and shortening decreased at lengths above FRC. The mean maximal velocity of shortening was 4.2 +/- 3.9% LR.S-1. We conclude that sonomicrometry may be used to record smooth muscle length in vivo. Vagal tone strongly influences passive length change. In vivo active shortening and velocity of shortening are less than in vitro, implying that there are significant loads impeding shortening in vivo.

Animals↗
PubMed2005

Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors.

PURPOSE: To evaluate long-term pulmonary toxicity of stereotactic radiotherapy (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small peripheral lung tumors. METHODS AND MATERIALS: A total of 17 lesions in 15 patients with small peripheral lung tumors, who underwent SRT between February 2000 and April 2003, were included in this study. Twelve patients had primary lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number of cigarettes smoked per day multiplied by number of years of smoking). Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8 fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test parameters included total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment-related factors, including age, the Brinkman index, internal target volume, the percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25, and V30, respectively), and mean lung dose. RESULTS: There were no significant changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from baseline in DLCO was significantly increased by 128.2%. Univariate and multivariate analyses revealed a correlation between DLCO and the Brinkman index. CONCLUSIONS: One year after SRT as compared with before SRT, there were no declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy smokers before SRT, suggesting a correlation between DLCO and smoking cessation. SRT seems to be tolerable in view of long-term lung function.

Aged↗
PubMed1993

Importance of inspiratory load in the assessment of severity of airways obstruction and its correlation with CO2 retention in chronic obstructive pulmonary disease.

Different aspects of mechanical loading were analyzed in a group of 25 patients with chronic obstructive pulmonary disease (COPD) who all had severe expiratory airflow limitation but different arterial CO2 values. It was found that the maximal expiratory flow rates (V75, V50, V25, VFRC), functional residual capacity (FRC), residual volume (RV), total lung capacity (TLC), specific airways conductance (SGaw) measured during inspiration or expiration, and lung recoil pressure (PLel) were not correlated to the PaCO2. Only five parameters were significantly linked to the PaCO2; they were the peak inspiratory flow (PIF) (r = -0.57, p < 0.002), the inspiratory vital capacity (IVC) (r = -0.46, p < 0.01), the maximal voluntary ventilation (MVV) (r = -0.49, p < 0.01), the total SGaw (r = -0.40, p < 0.03), and the forced expiratory flow volume in one second (FEV1) (r = -0.36, p < 0.05). It was concluded that the airflow limitation during the inspiratory phase has an important contribution to the CO2 retention in patients with COPD, and therefore analysis of both phases of the respiratory cycle is necessary to assess the severity of airway obstruction in this disease.

Aged↗
PubMed1994

Heterogeneous regional behavior during forced expiration before and after histamine inhalation in dogs.

We studied the evolution of alveolar pressure (PA) heterogeneity during the course of forced expiration in the lungs of six anesthetized open-chest dogs. Using an alveolar capsule technique, we measured PA simultaneously in six lung regions during full maximal forced deflations before and after administering aerosolized histamine. Flow was measured plethysmographically with volume obtained by flow integration. Heterogeneity was expressed as the coefficient of variation (CV) of regional PA after 25% of the vital capacity had been expired from total lung capacity. The CV in in vivo open-chest canine lungs (21.3%) was significantly greater than that we measured previously in excised lungs (8.7%) (P < 0.02). Inhalation of aerosolized solutions of histamine produced significant increases in interregional heterogeneity (CV = 35.5 and 38.8% after 3 and 10 mg/ml of histamine, respectively; P < 0.025). After histamine, the vital capacity was reduced and the configuration of the flow-volume curve demonstrated some shortening of the flow plateau commonly observed in dogs. Changes in the flow-volume relationship failed, however, to reflect well the marked degree of heterogeneity of PA after histamine administration. These findings may be reconciled on the basis of interdependence of regional expiratory flows. Reductions in flow from obstructed regions appear to be compensated by increases in flow from unobstructed regions and thus mask upstream nonuniformities. These mechanisms may explain in part why the maximal expiratory flow-volume curve has been a relatively insensitive tool for the detection of early nonuniform airway disease.

Administration, Inhalation↗