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PubMed2005

Quadriceps weakness is related to exercise capacity in idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: In COPD, it has been shown that peripheral muscle dysfunction is a factor determining exercise intolerance. We examined the hypothesis that exercise capacity of patients with idiopathic pulmonary fibrosis (IPF) is, at least in part, determined by peripheral muscle dysfunction. METHODS: Maximum oxygen uptake (V(O2)max) was evaluated in 41 consecutive patients with IPF, along with potential determinants of exercise capacity, both in the lungs and in the peripheral muscles. RESULTS: Patients had reduced V(O2)max (893 +/- 314 mL, 46.0% predicted) and reduced quadriceps force (QF) [65% predicted]. Significant correlates of V(O2)max reduction were vital capacity (VC) [r = 0.79], total lung capacity (r = 0.64), diffusion capacity (r = 0.64), QF (r = 0.62), maximum expiratory pressure (r = 0.48), and Pa(O2) at rest (r = 0.33). In stepwise multiple regression analysis, VC and QF were independent predictors of V(O2)max. Furthermore, in subgroup analysis, QF was a significant contributing factor for V(O2)max in patients who discontinued exercise because of dyspnea and/or leg fatigue. CONCLUSIONS: We conclude that QF is a predictor of exercise capacity in IPF. Measures that improve muscle function might improve exercise tolerance.

Aged↗
PubMed1985

Hyperoxia exposure in mechanically ventilated primates with and without previous lung injury.

The response of the injured lung to hyperoxia is uncertain. In the present study, we evaluated the effects of 100% oxygen exposure for 120-168 h in mechanically ventilated baboons with or without previous diffuse alveolar damage (DAD) induced by oleic acid. These two groups were compared with another group of six baboons previously studied in our laboratory in which DAD induced with oleic acid was followed by ventilation with 40% oxygen. Oleic acid infusion caused a prompt reduction in total lung capacity, static compliance, and diffusion capacity and an increase in lung tissue volume. The magnitude and course of oleic acid lung injury was similar for 4 days in animals breathing 100% or 40% O2. Animals breathing 100% O2 without previous lung injury developed significant decreases in total lung capacity, oxygenation, and diffusion capacity after 72 h of hyperoxia. By 120 h, lung function was similarly impaired in both 100% O2-breathing groups, and rapidly worsening pulmonary edema appeared radiographically between 5.5 and 7 days in all O2-exposed animals. Subsequent weaning was successful in only three animals after 100% O2 exposure. All but one animal in the 40% O2 group were easily weaned. Histologic changes between 6 and 14 days in 100% O2 animals showed a marked proliferative response, particularly of type 2 cells; no differences were found due to prior oleic acid injury. Resolution of this process occurred in a surviving animal, resulting in focal fibrotic residua at 6 weeks, similar to that observed in 40% O2 oleic acid-treated survivors. Previous lung injury due to oleic acid did not modify the response of the baboon lung to hyperoxia.

Animals↗
PubMed1986

Maximal static pressures and lung volumes in young female swimmers.

The postulate that lung volumes are increased in swimmers because of a training effect that increases maximal static pressures (Pmax) thus augmenting the ability to inflate and deflate the lung was examined by comparing 38 competitively trained female swimmers to 59 controls between 7 and 13 years of age. Maximal static pressures on inspiration and expiration were generated near residual volume (RV), at functional residual capacity (FRC) and near total lung capacity (TLC). Lung volumes were measured by body plethysmography. The expected increase in lung volumes was present in the swimmers and was most marked in the oldest subjects. However, training did not have the anticipated effect on Pmax. In the younger swimmers training was associated with an increase in Pmax, but in the older swimmers Pmax was actually decreased in comparison to controls. These findings suggest that training may directly enhance lung growth, since the changes in lung volume cannot be accounted for by increases in respiratory muscle strength.

Child↗
PubMed2000

Surfactant treatment impairs gas exchange in a canine model of acute lung injury.

UNLABELLED: The effectiveness of surfactant (SURF) treatment in acute lung injury in the adult is controversial. In this study, we tested the effectiveness of early surfactant treatment in a commonly used animal model of acute lung injury, phorbol-myristate acetate (PMA), to see if it would attenuate the progression of lung injury. We measured the effect on lung compliance and whether positive end-expiratory pressure (PEEP) (10 cm H2O) during SURF administration had a synergistic effect. METHODS: Four groups of anesthetized dogs were studied: a) normals; b) PMA injury only; c) PMA injury + SURF; and d) PMA + SURF + PEEP. Lung injury was induced with 25-30 microg/kg of PMA. Responses were measured over 7 hrs. Surfactant was administered in the form of Survanta, 4 x 25 mg/kg doses via tracheal instillation 2.5 hrs after PMA. For the group receiving PEEP, 10 cm H2O PEEP was begun 1.5 hrs after PMA, 1 hr before SURF. Postmortem, the left lung was excised and inflated three times to total lung capacity (volume at 30 cm H2O) and expiratory compliance was measured with 25-100 mL volume increments. The trachea was then clamped and trapped volume was determined by water displacement. RESULTS: PMA-induced lung injury significantly reduced expiratory compliance and total lung capacity (p < .05 from normal). Wet/dry lung weights did not differ between groups. SURF without PEEP further decreased lung compliance as compared with PMA only. CONCLUSIONS: SURF administration after PMA injury causes marked reductions in lung compliance when no PEEP is coadministered. However, the loss of static expiratory lung compliance appears partly ameliorated by application of PEEP + SURF. Given that tracheal instillation of SURF is known to acutely elevate lung impedance in the first few hours after administration, coadministration of PEEP appears to be critically important in counteracting these early effects of surfactant instillation on the lung.

Acute Disease↗
PubMed2003

Management of thoracic empyema in childhood: does the pleural thickening matter?

AIMS: To determine the clinical course and long term outcome of empyema treated without decortication. METHODS: Fourteen consecutive admissions to one hospital were studied; radiological resolution and lung function were subsequently followed. The children were aged 2-14 years. All were treated with intravenous antibiotics and chest drain only. RESULTS: All patients had extensive pleural thickening evident on chest x ray examination at the time of discharge, which resolved entirely over a period of 2-16 months. Lung function was measured in 13 children, and showed no evidence of restrictive or obstructive deficit: mean (SD) values as per cent predicted for height were: forced expiratory volume in one second (FEV1) 107.5 (9.6), forced vital capacity (FVC) 95.5 (8.8), total lung capacity (TLC) 98.6 (20.7). Individual children all had values in the normal range (80-120 per cent predicted). CONCLUSION: Results suggest that decortication is not necessary in children to prevent long term problems with pleural thickening, and should be undertaken on the basis of the clinical picture (failure of fever resolution), rather than radiological appearance.

Adolescent↗
PubMed1987

Geometry and respiratory displacement of human ribs.

The three-dimensional coordinates of points in the ribs of two supine relaxed males, holding their breath at functional residual capacity (FRC) and with their glottis closed at total lung capacity (TLC), were obtained from volumetric X-ray computed tomographical images. The orientation of planes that best fit the data for each rib at each lung volume and the circular arcs that fit the points in the planes of the ribs were determined, and average values of these geometrical parameters for ribs 3-7 are reported. The planes of the ribs at TLC can be described as displaced from the planes at FRC by a rotation about an axis that passes near the spine. The pump handle and bucket handle components of rotation are 11 and 13 degrees, respectively, for rib 3 and both decrease with increasing rib number to 7 and 10 degrees at rib 7. The angles between the axes of rotation and the midplane are approximately 35 degrees for all 5 ribs. The radii of the circular arcs fit to the data at TLC are slightly larger than those at FRC, and this suggests that there is a small component of rotation normal to the plane of the rib.

Adult↗
PubMed1980

Regression of lung size in adults with growth hormone deficiency.

Pulmonary function was investigated in eight patients with hypopituitarism in order to determine if the lung is affected by the generalized visceral atrophy of hypopituitarism; six patients with acromegaly and trophic hormone deficiencies were studied for comparison. The patients with hypopituitarism, including one with isolated growth hormone (GH) deficiency, had a restrictive type of ventilatory impairment (total lung capacity was 76.7 +/- 4.7 per cent of predicted, p less than 0.005) which was not influenced by cortisone, thyroxine or sex hormone replacement therapy. In contrast, the patients with acromegaly, despite deficiency of one or more pituitary hormones, had larger lungs than controls (total lung capacity was 119.5 +/- 5.0 per cent of predicted, p less than 0.01). These findings indicate that GH influences the lung volume in adult man and that the loss of GH secretion is likely to be responsible for the restrictive ventilatory impairment associated with hypopituitarism. Further studies showed that this restrictive defect was not related to neuromuscular impairment or to an abnormality of chest wall mechanics, and suggested that the ventilated air spaces retained normal elastic properties. It appears that a decrease in lung size occurs in patients who develop GH deficiency and thus, that normal levels of GH are necessary for maintaining normal lung size during adult life.

Acromegaly↗
PubMed1980

Single-breath diffusing capacity and lung volumes in small laboratory mammals.

We measured the single-breath diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) in anesthetized male hamsters, rats, guinea pigs, and rabbits whose weights varied from 40 to 3,500 g. TLC (defined as an airway pressure of 25 cmH2O) was calculated by neon dilution. The DLCO was estimated by a modification of the single-breath method. There was a high correlation between body weight and our measurement of both the diffusing capacity and the lung volumes. No significant difference in DLCO was observed in rats when measured in different body positions, at airway pressures of 10 or 20 cmH2O, from FRC or RV, in male or female rats, or following hyperventilation.

Animals↗
PubMed1986

Effect of prolonged bed rest on lung volume in normal individuals.

Pulmonary function was assessed in supine subjects before, during, and after three separate bed-rest studies of 11 and 12 days duration. Forced vital capacity (FVC) increased during bed rest in each subject. Total lung capacity (TLC) was measured by helium dilution in one bed-rest study and increased in each subject, while residual volume and functional residual capacity of the respiratory system did not change. No change in FVC was found in an ambulatory control group using identical measurement techniques. Maintaining base-line plasma volume during one bed rest by the use of exogenous estrogen did not prevent an increase in FVC, and decreasing plasma volume with diuretics in ambulatory subjects to the same degree as seen in the bed rests did not cause an increase in FVC. We conclude that prolonged bed rest results in a small significant increase in TLC and that this change is not dependent on alterations in plasma volume.

Adult↗
PubMedDate not supplied

Who waits longest for heart and lung transplantation?

Between August 1982 and December 1992, 260 patients were accepted for heart and lung transplantation, of whom 139 patients underwent transplant surgery. One hundred twenty-one patients have not received transplants, of whom 80 have died, four were transferred to other lists, and 37 were still waiting for suitable organs at the close of the study. Median waiting time for those patients who underwent heart and lung transplantation was 7 months, whereas patients who died waiting spent a median of 5 months on the list. Recipients are matched to donor organs according to blood type, size (total lung capacity), and cytomegalovirus antibody status. These factors, along with age, gender, underlying diagnosis, and Toxoplasma antibody status, were studied to assess their influence on survival after acceptance and time to transplantation. The only characteristic that significantly influenced survival after acceptance was the underlying disease, with patients with Eisenmenger's syndrome having significantly longer survival than the other groups (relative risk = 0.21; p < 0.001). Patients with Eisenmenger's syndrome underwent transplantation at a slower rate than did other patients (relative risk = 0.51; p = 0.012). Patients who had a total lung capacity of more than 6 L underwent transplantation significantly more quickly than did smaller patients (relative risk = 1.98; p = 0.005). Male patients underwent heart and lung transplantation at a quicker rate than did female patients (relative risk = 1.86; p < 0.001), although this was related to size. Patients who had cytomegalovirus-positive antibodies underwent transplantation at almost twice the rate of patients who had cytomegalovirus-negative antibodies (relative risk = 1.92; p < 0.001). Age at acceptance, blood type, and Toxoplasma status did not significantly influence time to heart and lung transplantation. In summary, cytomegalovirus antibody status, patient size, and gender significantly affect the waiting time to heart and lung transplantation. Patients with Eisenmenger's syndrome wait longer than other patients as a result of the natural history of their disease.

Adolescent↗
PubMed1993

Blood gas dynamics at the onset of exercise in heart transplant recipients.

One hypothesis to explain the rapid neural component of exercise hyperpnea contends that afferent stimuli originating in the ventricles of the heart act reflexly on the respiratory center at the onset of exercise, ie, "cardiodynamic hyperpnea." Orthotopic cardiac transplantation (Tx) results in the loss of afferent information from the ventricles. Thus, Tx possibly results in transient hypercapnia and hypoxemia in deafferented heart transplant recipients (HTR) at the onset of exercise due to hypoventilation. To examine the cardiodynamic hypothesis, we collected serial arterial blood gas (ABG) samples during both the transient and the steady-state responses to moderate cycle exercise in 5 HTRs (55 +/- 7 years) 14 +/- 7 months post-Tx and 5 control subjects matched with respect to gender, age, and body composition. Forced vital capacity, forced expiratory volume in 1 s, total lung capacity, and diffusion capacity did not differ (p > or = 0.05) between groups. Resting arterial PO2, PCO2, and pH did not differ between groups (p > or = 0.05). The ABGs were drawn every 30 s during the first 5 min and at 6, 8, and 10 min of constant load square wave cycle exercise at 40 percent of the peak power output (watts). Absolute and relative changes in arterial PO2, PCO2, and pH were similar (p > or = 0.05) between HTR and the control group at all measurement periods during exercise. Heart rate (%HRmax reserve), rating of perceived exertion, and reductions in plasma volume (% delta from baseline) did not differ between HTR and control during exercise at 40 percent of peak power output (p > or = 0.05). Our results demonstrate that there is no discernible abnormality in ABG dynamics during the transient response to exercise at 40 percent of peak power output in patients with known cardiac denervation. These data do not support the cardiodynamic hyperpnea hypothesis of ventilatory control in humans. The absence of hypercapnia in HTRs is further evidence for the existence of redundant mechanisms capable of stimulating exercise hyperpnea.

Adult↗
PubMed1999

Static lung volumes: reference values from a Latin population of Spanish descent.

BACKGROUND AND OBJECTIVES: The aim of this study was to develop a set of prediction equations and 90% confidence intervals for static lung volumes using the multibreath helium equilibration method from a sample of asymptomatic Caucasian subjects of Spanish descent. Moreover, these equations were compared with those of previous studies. METHODS: Measurements of static lung volumes using techniques recommended by the American Thoracic Society and the European Community for Steel and Coal were carried out on a selected sample of 591 healthy nonsmoking volunteers (305 men and 286 women) aged 18-88 years, living in the metropolitan area of Valencia, on the east coast of Spain. Multiple regression analysis using height, age and weight as independent variables were used to provide predicted values for both sexes. These reference values were compared with other sets of prediction equations reported in the literature using an independent sample of 69 subjects (32 men and 37 women). RESULTS: Simple linear regression equations using age, height and body weight predicted all the subdivisions of lung volumes (vital capacity, expiratory reserve volume (ERV), inspiratory capacity, functional residual capacity (FRC), residual volume (RV), total lung capacity (TLC), FRC/TLC and RV/TLC) as well as more complex equational models. The distribution of residuals fulfilled the assumptions of multiple regression analysis (independence, homoscedasticity and Gaussian distribution of residuals), except for ERV, using simple linear models. The derived equations did not differ significantly from most of the previously reported equations and were usually superior in their ability to predict the lung volumes. CONCLUSIONS: The use of the present prediction equations is recommended in the Latin population of Spanish descent and in populations with similar Caucasian characteristics.

Adolescent↗
PubMed1998

Myosin heavy chain gene expression changes in the diaphragm of patients with chronic lung hyperinflation.

In striated muscle, chronic increases in workload result in changes in myosin phenotype. The aim of this study was to determine whether such changes occur in the diaphragm of patients with severe chronic obstructive pulmonary disease, a situation characterized by a chronic increase in respiratory load and lung volume. Diaphragm biopsies were obtained from 22 patients who underwent thoracic surgery. Myosin was characterized with electrophoresis in nondenaturing conditions, SDS-glycerol PAGE, and Western blotting with monoclonal antibodies specific for slow and fast myosin heavy chain (MHC) isoforms. Flow volume curves, total lung capacity, and functional residual capacity were measured before surgery in 20 patients. We found that the human diaphragm is composed of at least four myosin isoforms, one slow and three fast, resulting from the combination of three MHC species. Chronic overload was associated with an increase in the slow beta-MHC species at the expense of the fast species (beta-MHC, 78.2 +/- 4.6 and 50.0 +/- 6.5% in emphysematous and control patients, respectively; P < 0.005). Linear correlations were found between beta-MHC percentage and forced expiratory volume in 1 s (r = -0.52; P < 0.02), total lung capacity (r = 0.44; P < 0.05), and functional residual capacity (r = 0.65; P < 0.003). The human adult diaphragm is composed of a balanced proportion of slow and fast myosin isoforms. In patients with chronic obstructive pulmonary disease, the proportion of fast myosins decreases, whereas that of slow myosin increases. This increase appears to be closely related to lung hyperinflation and may reflect an adaptation of the diaphragm to the new functional requirements.

Adult↗
PubMed1998

Comparison of the functional results of single lung transplantation for pulmonary fibrosis and chronic airway obstruction.

BACKGROUND: Single lung transplantation (SLT) is now a treatment option for patients with both pulmonary fibrosis and advanced chronic airway obstruction. Lung function after transplantation might be expected to be different in these two groups of patients because of the effect of the remaining native lung, but the implications of these differences have not been fully explored. METHODS: The functional results of a stable population of 20 patients (13 chronic airway obstruction, seven pulmonary fibrosis) after SLT with no evidence of obliterative bronchiolitis were analysed. The differences between the two populations in the interrelations between and determinants of total lung capacity (TLC), subdivisions of lung volume, airway function (spirometry, maximum expiratory flow volume curves, and moments analysis of the spirogram) respiratory mechanics (PV curves and maximal respiratory pressures), CO transfer factor (TLCO) and the distribution of perfusion, ventilation and volume of the transplanted and native lungs were compared. RESULTS: Total lung capacity after SLT (TLCpost) was normal in the patients with pulmonary fibrosis (mean (SE) 103.9 (6.9)% predicted) but remained significantly elevated in patients with airway obstruction (126.4 (4.4)%. Forced expiratory volume in one second (FEV1) and vital capacity (VC) improved to similar values after SLT in both groups with a final VC of 76.8 (5.9)% and 66.7 (3.9)% in patients with fibrosis and airway obstruction, respectively. Maximum expiratory flows were generally lower and moments analysis of the spirogram showed slower lung emptying with significantly greater second and third moments (alpha 2 and alpha 3) in patients with airway obstruction. Relative ventilation and perfusion of the transplanted lung were both greater in both populations but relative ventilation of the transplanted lung was significantly greater in patients treated for airway disease than in those with pulmonary fibrosis. TLCO was also significantly higher in patients who had received a transplant for chronic airway obstruction. CONCLUSIONS: These results suggest that differences in the functional results of SLT for airway disease and pulmonary fibrosis are relatively minor. In this series the native hyperinflated lung in chronic airway disease was not more disadvantageous to overall function than the native lung in pulmonary fibrosis. However, tests of lung function based on the terminal portion of the forced spirogram are likely to be less sensitive for the detection of obliterative bronchiolitis in patients who have received a transplant for advanced airway obstruction than in those with pulmonary fibrosis.

Female↗
PubMed1986

The relationship between alveolar oxygen tension and the single-breath carbon monoxide diffusing capacity.

The effects of alveolar oxygen tension (PAO2) on the single-breath carbon monoxide diffusing capacity (DLCO) were quantified and a factor was derived to accommodate for differences in PAO2 over commonly encountered altitudes and/or varying concentrations of oxygen in the test gas mixture (FIO2) We performed duplicate measurements of DLCO in 7 normal subjects with 6 different oxygen fractions (0.176, 0.196, 0.211, 0.22, 0.25, and 0.27). The PAO2 for each test was measured as the PO2 in the alveolar gas sample bag. DLCO varied inversely with PAO2 and changed by 0.35% for each mmHg change in PAO2 (r = -0.62, p less than 0.001). At an FIO2 of 0.25, PAO2 varied between subjects and was highly correlated with each subject's residual volume to total lung capacity ratio (r = -0.84, p less than 0.001). We suggest that laboratories can adjust the measured DLCO when PAO2 is not congruent to 120 mmHg by the following formula: DLCO (corrected = DLCO (measured) x [1.0 + 0.0035 (PAO2 - 120)].

Adult↗
PubMed1981

Comparison of ventilation/perfusion lung-imaging and dead-space measurements in airway disease.

1. Nineteen patients (three normal subjects, at 16 patients with chronic airway disease) were investigated with radionuclide lung-imaging and pulmonary function tests. 2. There was a statistically significant correlation between the ratio of residual volume to total lung capacity and alveolar dead-space ventilation for nitrogen as a percentage of alveolar ventilation (an index of gas mixing inefficiency); rs = 0.54, P less than 0.05. 3. There were statistically significant associations between an abnormal ventilation or perfusion radionuclide lung image and (a) the ratio of residual volume to total lung capacity and (b) the alveolar dead-space ventilation for nitrogen as a percentage of alveolar ventilation. 4. The radionuclide counts from the posterior images were normalized for lung size and injected dose; perfusion counts were then subtracted from ventilation counts at locations from the top to the bottom of the lungs. 5. There was a statistically significant association between low ventilation minus perfusion areas and arterial hypoxia. 6. There was a statistically significant association between high ventilation minus perfusion areas and an increased alveolar dead-space ventilation for carbon dioxide as a percentage of alveolar ventilation.

Adult↗
PubMed2005

Idiopathic pulmonary fibrosis in patients younger than 50 years.

OBJECTIVE: To assess clinical, radiological, histopathologic, and prognostic differences in younger patients with idiopathic pulmonary fibrosis (IPF). PATIENTS AND METHODS: This study consisted of patients younger than 50 years with IPF who were seen at the Mayo Clinic in Rochester, Minn, from January 1, 1994, to December 31, 2000. Clinical, radiological, and histopathologic data were abstracted from clinical records. Total lung capacity using plethysmography, vital capacity, diffusing capacity for carbon monoxide using the single-breath method, and alveolar volume using single-breath neon wash-in were measured. RESULTS: Our study population was composed of 16 men and 6 women with a median age of 45 years (range, 28-49 years). Median survival was 2.1 years, with 1- and 2-year survival rates of 68% and 53%, respectively. Of the 22 patients, 2 were current smokers, 14 were former smokers, and 6 had never smoked. Three patients had familial pulmonary fibrosis, 21 had bibasilar inspiratory crackles, and 10 had digital clubbing. Median total lung capacity was 56.2%, vital capacity was 51.0%, diffusing capacity was 45.5%, and alveolar volume was 65.0%. CONCLUSION: Although previous studies have suggested that younger age is a favorable prognostic factor in patients with IPF, we found that younger patients have the same poor prognosis as do older patients with this disorder. We observed no distinguishing differences in the clinical, radiological, and histopathologic features compared with those in older patients in whom the disorder is more common. Lung transplantation should be considered early in the treatment of younger patients with IPF.

Adult↗
PubMed2002

Persistent abnormal lung function after childhood empyema.

OBJECTIVE: The purpose of this study was to examine pulmonary function tests in children at various time points in their recovery from empyema. DESIGN: Cross-sectional study. SETTING: Academic Children's Hospital. PATIENTS: Pediatric patients with a diagnosis of empyema between 1992-2000. RESULTS: A total of 45 pulmonary function tests were carried out in 36 study participants. Within 3 months of hospital discharge, 91% of pulmonary function tests demonstrated a restrictive pattern with a mean forced vital capacity (FVC) of 69.2 +/- 4% and a mean total lung capacity (TLC) of 74.9 +/- 4% of predicted. The incidence of restriction in pulmonary function significantly decreased over time and for patients tested > 1 year from hospital discharge the mean FVC was 87.1 +/- 2% and the mean TLC 95.0 +/- 2% of predicted. However, 19% of the patients tested > 1 year from discharge demonstrated a mild restrictive pattern and 16% demonstrated a mild obstructive changes. Patients with abnormal lung function > 1 year from hospital discharge did not demonstrate any signs or symptoms of respiratory insufficiency . CONCLUSION: There is a high incidence of restrictive patterns in lung function for children tested within 3 months from hospital discharge for empyema. The incidence of restrictive patterns decreased significantly over time and most patients tested >1 year from hospital discharge demonstrated normal lung function.

Adolescent↗