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Clinical trial of a modified inhaler for pressurized aerosols.

Using spirometry, the effects on lung function of interposing a tube extension between a bronchodilator aerosol (terbutaline sulphate 0.25 mg) and the mouth and an ordinary aerosol have been compared. Both devices were administered with a delay of 2 s from actuating the aerosol to inhalation, thus simulating inability to coordinate properly. In 12 stable asthmatics it was found that attachment of the tube extension to the aerosol gave significantly better results for one-second forced vital capacity (FEV1.0) and forced vital capacity (FVC). The tube extension seems to be beneficial in patients with hand-lung dyscoordination.

Adult↗

Coronal and sagittal plane spinal deformities correlating with back pain and pulmonary function in adult idiopathic scoliosis.

One hundred one referred adult patients (ages 20-63; mean, 36 years) with painful idiopathic scoliosis were evaluated. None had prior surgical treatment. Severity of pain was graded and localized over radiographic deformities in the coronal and sagittal planes. Radiographic changes in primary as well as full and fractional compensatory curves were studied. Degrees of scoliosis, percent correction on side bending, vertebral body rotation at curve apex, spinal balance, and lateral olisthesis in the coronal plane, degenerative disc disease, and other degenerative changes in all curves were measured and graded in both the coronal and sagittal planes. Lordosis and kyphosis were measured on all standing sagittal radiographs. Forty-one patients had pulmonary function studies. Multiple variable statistical analysis (Spearman correlation coefficients) of the data found fractional lumbosacral curves most painful and disabling. Scoliosis greater than 40 degrees and kyphosis greater than 50 degrees correlated with increasing pain and decreasing forced vital capacity. Reduction in forced vital capacity also correlated with curve rigidity. Rotation correlated closely with degrees of scoliosis (r = 0.70; P less than 0.0001) and had the highest correlation with pain (r = 0.59; P less than 0.0001) of all radiographic findings and deformities studied.

Adult↗

Assessment and monitoring of flow limitation and other parameters from flow/volume loops.

Flow/volume (F/V) spirometry is routinely used for assessing the type and severity of lung disease. Forced vital capacity (FVC) and timed vital capacity (FEV1) provide the best estimates of airflow obstruction in patients with asthma, chronic obstructive pulmonary disease (COPD) and emphysema. Computerized spirometers are now available for early home recognition of asthma exacerbation in high risk patients with severe persistent disease, and for recognition of either infection or rejection in lung transplant patients. Patients with severe COPD may exhibit expiratory flow limitation (EFL) on tidal volume (VT) expiratory F/V (VTF/V) curves, either with or without applying negative expiratory pressure (NEP). EFL results in dynamic hyperinflation and persistently raised alveolar pressure or intrinsic PEEP (PEEPi). Hyperinflation and raised PEEPi greatly enhance dyspnea with exertion through the added work of the threshold load needed to overcome raised pleural pressure. Esophageal (pleural) pressure monitoring may be added to VTF/V loops for assessing the severity of PEEPi: 1) to optimize assisted ventilation by mask or via endotracheal tube with high inspiratory flow rates to lower I:E ratio, and 2) to assess the efficacy of either pressure support ventilation (PSV) or low level extrinsic PEEP in reducing the threshold load of PEEPi. Intraoperative tidal volume F/V loops can also be used to document the efficacy of emphysema lung volume reduction surgery (LVRS) via disappearance of EFL. Finally, the mechanism of ventilatory constraint can be identified with the use of exercise tidal volume F/V loops referenced to maximum F/V loops and static lung volumes. Patients with severe COPD show inspiratory F/V loops approaching 95% of total lung capacity, and flow limitation over the entire expiratory F/V curve during light levels of exercise. Surprisingly, patients with a history of congestive heart failure may lower lung volume towards residual volume during exercise, thereby reducing airway diameter and inducing expiratory flow limitation.

Asthma↗

Physical training during intrahepatic chemotherapy.

OBJECTIVE: To evaluate the role of strength and endurance training for the muscular, cardiac, respiratory, and immune systems and the quality of life (QOL) during intrahepatic chemotherapy (folinic acid, 5-fluorouracil). DESIGN: Single case. SETTING: Teaching hospital in Germany. PARTICIPANT: An elderly athlete with liver metastasis after resection of a carcinoma of the rectum (pT3, N0, M-liver, G2). INTERVENTION: Strength and endurance training during chemotherapy. MAIN OUTCOME MEASURES: During the intervals between training cycles (14d), beginning in postoperative week 6, a strength and endurance training regimen was performed twice weekly for 13 weeks, with an intensity of 40% to 60% of the maximum postoperative individual power and endurance. Before and after chemotherapy, we checked echocardiograms, resting and exercise electrocardiograms, lung function, natural killer (NK) cells, and the Gastrointestinal Quality of Life Index (GIQLI) scores. RESULTS: The increase in strength was between 0% and 144%. The improvement in endurance expressed by reduction of heart rate and lactate concentration was 10% and 21.5%, respectively. Lung function also improved with regard to forced expiratory volume in 1 second (12.9%), forced vital capacity (11.3%), and inspiratory vital capacity (11.4%). The relative count of the NK cells increased to 27.2%. An improvement in the GIQLI was observed from 109 points (pathologic) to 129 points. CONCLUSION: Strength and endurance training was associated with an increase of physical strength and endurance with positive influence on illness-related QOL. Postoperative physical exercise during regional chemotherapy is beneficial.

Adenocarcinoma↗

A device for overcoming discoordination with metered-dose inhalers.

BACKGROUND: Despite widespread acceptance of metered-dose inhalers (MDIs) in the treatment of asthma, many patients fail to operate these devices correctly. Inability to properly coordinate activation with onset of inhalation is regarded as the major factor in suboptimal MDI therapy. METHODS: We evaluated Autohaler Inhalation Device (3M Pharmaceuticals, St. Paul, Minn.), a breath-activated MDI that is typically activated at a triggering flow rate of approximately 0.5 L/sec. We compared bronchodilator effect of pirbuterol acetate (Maxair), inhaled from Autohaler and a standard MDI, under conditions that ensured optimal technique in 20 patients with asthma. Spirometric variables (forced expiratory volume in 1 second [FEV1], forced expiratory flow between 25% and 75% of vital capacity [FEF25-75], forced vital capacity [FVC]) were measured before and at 15, 30, 60, and 90 minutes after two inhalations of full inspiratory reserve volume for each device. RESULTS: Both devices produced significant and similar bronchodilation. Mean FEV1 increased 32% above baseline 60 minutes after use of Autohaler and 31% after use of a standard MDI. Similar changes were noted in FEF25-75 and FVC for the two devices. Differences between devices for all spirometric variables were not statistically significant. CONCLUSION: Autohaler provides a promising alternative to the standard MDI by overcoming breath-hand discoordination.

Adolescent↗

Influence of thoracoabdominal movement on pulmonary function in patients with Parkinson's disease: comparison with healthy subjects.

Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoabdominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiratory inductance plethysmography by fixing transducers on the rib cage and umbilicus. Patients with PD had significantly decreased % VC (90.3 +/- 17.1 vs 105.8 +/- 13.9%), chest movement (271.3 +/- 79.6 vs. 375.2 +/- 126.7% VT) and abdominal movement (217.6 +/- 93.5 vs. 247.4 +/- 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had significantly decreased % FVC (74.4 +/- 20.6 vs. 97.6 +/- 14.1%), chest movement (246.2 +/- 115.2 vs. 344.5 +/- 126.4% VT) and abdominal movement (160.3 +/- 105.6 vs 207.6 +/- 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with abdominal movement in patients with PD.

Abdomen↗

[Normal values of spirometry for the 15- to 20-year-old age group].

In 130 healthy young men and women aged 15 to 20 years, all non-smokers, volume flow curves were recorded during forced expiratory vital capacity measurements. The forced vital capacity (FVC), the forced expiratory volume of 1 sec (FEV1) and the mid-expiratory flow rate (MEF50) were evaluated in order to establish new standard values for normal people in this particular age group. FVC is strongly height and sex dependent. Our new normal values are in good agreement with those of the literature. Our FVC values, however, are in general slightly higher than those of previous authors. MEF50 turns out to be sex independent but height dependent, but not as much as FVC. Our new normal values for MEF50 are in good agreement with those of Knudson et al., though slightly lower. The FEV1/FVC quotient was found to decrease significantly with height from 0.9 to 0.8. This decrease may be due to the increase in lung volume with growth. It could also be due to lung damage caused by atmospheric air pollution in young adults who are still growing.

Adolescent↗

Dust exposure and impairment of lung function at a small iron foundry in a rapidly developing country.

OBJECTIVES: A cross sectional prospective study was carried out among iron foundry workers (exposed) and soft drink bottling and supply company workers (unexposed) to assess their occupational exposure to ambient respiratory dust in their work environment and its effect on their lung function profile. PARTICIPANTS: Lung function was measured in 81 exposed and 113 unexposed workers. Personal respirable dust concentrations were measured for all the exposed and the unexposed workers. Information on respiratory signs and symptoms was also collected from the participants. RESULTS: Among the exposed workers, midexpiratory flow (FEF25-75), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), FEV1/FVC, and FEV1/VC ratios were significantly lower whereas the vital capacity (VC) and forced vital capacity (FVC) were non-significantly higher. Job at the iron foundry was a significant predictor of lung function. Exposure to high concentration of respirable dust at the iron foundry was also a significant predictor. Workers working in high exposure areas (general works, furnace, continuous casting areas, and fabrication workshop) had lower lung function values than workers in medium and low exposure areas. Smoking did not enhance the effects of exposure to dust on lung function. CONCLUSIONS: Exposure to respirable dust was higher among the iron foundry workers; and among these, general, furnace, rolling mill, and fabrication workers had higher exposures to dust than did workers in continuous casting, the mechanical workshop, and the bottling plant. Job type and exposure to dust were significant predictors of lung function. Implementation of industrial hygiene and proper and efficient use of personal protection equipment while at work could help to protect the respiratory health of industrial workers.

Case-Control Studies↗

Clinical comparison of albuterol, isoetharine, and metaproterenol given by aerosol inhalation.

The clinical effectiveness of albuterol, isoetharine, and metaproterenol administered by aerosol inhalation at manufacturer-recommended doses was compared. A double-blind, placebo-controlled, crossover comparison of albuterol 280 micrograms, isoetharine 680 micrograms, and metaproterenol 1300 micrograms was conducted in 10 adult men with reversible, chronic pulmonary obstruction. FEV1 (forced expiratory volume at one second), FEF25-75 (forced expiratory flow rate from 25 to 75% of vital capacity), and FVC (forced vital capacity) were determined periodically for six hours after drug administration. Bronchodilator effects, adverse effects, and cost of treatments were compared. Theophylline therapy was unaltered during the study, and serum theophylline concentration was determined periodically to control for its effect on pulmonary function. Serum theophylline concentration was not used as a covariate since it resulted in minimal change in the pulmonary-function measures. The mean maximum percent change from baseline for FEV1 for each drug was superior to placebo; there were no differences among drugs. Comparing area under the curve of mean percent change in FEV1 versus time, albuterol and metaproterenol produced changes that were greater than placebo but not different from each other or isoetharine. For FEF25-75 and FVC, albuterol and metaproterenol, respectively, were superior. No pattern of adverse effects was identifiable among the four treatments. The average wholesale cost of albuterol products was approximately 1.7 times the cost of metaproterenol products. Under the conditions of this study, metaproterenol was superior to isoetharine and therapeutically equivalent to and less expensive than albuterol.

Aerosols↗

Lung function, haemoglobin and irreversibly sickled cells in sickle cell patients.

This study seeks to show whether there is a positive relationship between HbF, irreversibly sickled cells and several lung function parameters. Percentage haemoglobin F (%HbF), percent irreversibly sickled cells (%ISC), blood pressure (BP, mm Hg), heart rate (HR, b/min), forced vital capacity (FVC,I), timed vital capacity (FEV1, I) FEV1% and peak expiratory flow rate (PEFR, I/min) were measured in 10 sickle cell (in the steady state) and 15 non-sickle cell subjects matched by age and sex. Results showed that although the ages in both groups of subjects were similar, sickle cell anaemia (SCA) subjects had smaller stature. Diastolic BP was significantly lower while pulse pressure, %Hbf and %ISC were significantly higher in SCA subjects (P < 0.001 in each case). Predicted FVC, FEV1, and PEFR were significantly higher (P < 0.01, P < 0.01, P < 0.001 in each case) than observed values obtained from SCA subjects. Similarly, measured FVC, FEV1, and PEFR in SCA subjects were significantly lower (P < 0.001 respectively) than values obtained from non-sickle cell subjects. In SCA subjects, %HbF or %ISC correlated negatively with each of the ventilatory parameters and with each other. Similar results (except for PEFR) were obtained in the non-sickle cell subjects. The results suggest that %HbF and %ISC correlate negatively with lung function parameters in sickle cell sufferers in the steady state.

Adolescent↗

The assessment of lung function in children with scoliosis.

Abnormalities of lung function in 92 children with idiopathic or congenital scoliosis are described. The changes are restrictive in type with reduction in vital capacity and total lung capacity but normal residual volume. In children whose curves had an early onset, the amount by which vital capacity was reduced depended on the severity of the deformity; in those whose curves began in adolescence this severity had little or no effect on vital capacity. Most adolescents with idiopathic curves had normal or near normal lung volumes and measurement of vital capacity proved to be a reliable screening test. We therefore advocate a simple approach to the pre-operative pulmonary investigation of scoliotic patients; only a few require full spirometry.

Adolescent↗

High thoracic epidural anesthesia does not alter airway resistance and attenuates the response to an inhalational provocation test in patients with bronchial hyperreactivity.

BACKGROUND: The functional relevance of an intact pulmonary sympathetic innervation for airway resistance is unknown. We therefore evaluated whether or not pulmonary sympathetic denervation by thoracic epidural anesthesia decreases the threshold of an inhalational provocation with acetylcholine in 20 patients with documented bronchial hyperreactivity scheduled for elective upper abdominal or thoracic surgery. METHODS: Baseline inhalational provocation with acetylcholine was performed 2-4 days before surgery. The acetylcholine threshold concentration for a hyperreactivity response (i.e., for a 20% decrease in forced expiratory volume in 1 s and a 100% increase in total respiratory resistance by oscillometry) was determined. On the day of surgery a second inhalative provocation with acetylcholine was performed 45 min after the patients had received 6-8 ml epidural bupivacaine 0.75% (n = 10), intravenous bupivacaine (1.2 mg.min-1, n = 6), or 6-8 ml epidural saline (n = 4). The acetylcholine threshold concentration for a hyperreactive response was again determined. We also measured vital capacity, forced expiratory volume in 1 s as a percentage of vital capacity, spread of sensory blockade (pin prick), skin temperature on hand and foot (telethermography). RESULTS: During thoracic epidural anesthesia, C4-T8 skin temperature increased significantly on hand and foot indicating widespread sympathetic blockade including the lungs. Compared to values obtained immediately before pulmonary sympathetic blockade, forced expiratory volume in 1 s as a percentage of vital capacity, and total respiratory resistance by oscillometry remained unchanged, while vital capacity decreased. Compared to baseline the acetylcholine threshold concentration for the hyperreactive response increased threefold after epidural as well as after intravenous bupivacaine. Epidural saline evoked no directional changes in the acetylcholine threshold concentration. CONCLUSIONS: We conclude that in patients with bronchial hyperreactivity 1. blockade of pulmonary sympathetic innervation seems to be of no relevance for airway resistance and 2. both epidural and intravenous bupivacaine substantially attenuate the response to an inhalational provocation with acetylcholine.

Acetylcholine↗

Late effects of bone marrow transplantation on pulmonary function in children.

This study was undertaken to evaluate in a primarily pediatric population whether the late effects of bone marrow transplantation (BMT) on pulmonary function in patients having undergone the procedure for treatment of acute leukemia or lymphoma are worse than that of patients having undergone transplant for treatment of aplastic anemia. Forty-six patients were studied. We did not demonstrate statistically significant differences in group mean forced expiratory flow in one second/forced vital capacity (FEV1/FVC) and percentage predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% of the forced vital capacity (FEF25-75) and total lung capacity (TLC) values between the two groups of patients before BMT and to 7 years post-transplant. Individual patients with pulmonary function abnormalities were identified. Furthermore, there were no significant differences between the two study groups or within the group of patients with aplastic anemia from pre-transplant to 9-12 months and from pre-transplant to 18-24 months after BMT. However, within the group of patients treated for acute leukemia or lymphoma, there was a significant decline in the group mean percentage predicted FVC (p = 0.0001), FEV1 (p = 0.0006) and FEF25-75 (p = 0.0063) from pre-transplant to 9-12 months and in the FVC (p = 0.004) and FEV1 (p = 0.0006) from pre-transplant to 18-24 months after BMT. The greater decline in the FVC relative to the FEV1 suggests the development of a restrictive process in this group of patients.

Adolescent↗

The role of preoperative pulmonary function tests in the surgical treatment of scoliosis.

STUDY DESIGN: A retrospective study on the correlation between preoperative pulmonary function tests, preoperative pulmonary symptoms, and postoperative pulmonary complications. OBJECTIVE: To evaluate the incidence of immediate postoperative pulmonary complications and their correlation to pulmonary function tests, preoperative pulmonary symptoms, and surgical approaches. SUMMARY OF BACKGROUND DATA: The pulmonary function of patients with scoliosis is likely to be abnormal, whereas surgical procedures may lead to further deterioration and postoperative pulmonary complications. Evaluation of the pulmonary symptoms and pulmonary function before surgery is helpful to predict and avoid postoperative pulmonary complications by selecting the appropriate surgical approach. METHODS: This study reviewed 298 scoliosis patients (107 male, 191 female) who underwent anterior and/or posterior operation. The mean age of the patients was 16.4 years (range 6-62 years). The average coronal Cobb angle was 73.26 degrees (range 45-141 degrees). Preoperative pulmonary function tests of 115 cases were normal, whereas the other 183 cases were abnormal. Seventeen cases had preoperative pulmonary symptoms and 3 of them had normal preoperative pulmonary function tests. Seventy-nine cases received transthoracic surgery, and 19 cases had postoperative pulmonary complications, including postoperative ventilation support in 6 cases, atelectasis in 4 cases, hydrothorax in 2 cases, pneumothorax in 3 cases, pneumonia in 3 cases, and hypoxemia in 1 case. Of these 19 patients, 12 patients received anterior transthoracic procedure. When the patients with abnormal pulmonary function tests were divided into 3 groups: 1) 60% < or = forced vital capacity ratio < 80%; 2) 40% < or = forced vital capacity ratio < 60%; and 3) forced vital capacity ratio < 40%, the incidence of postoperative pulmonary complications were 2.72% (3 out of 110), 7.40% (4 out of 54) and 31.60% (6 out of 19), respectively. RESULTS: There was significant correlation between abnormal preoperative pulmonary function tests and preoperative pulmonary symptoms (P = 0.0086). No significant correlation was found between preoperative pulmonary symptoms and postoperative pulmonary complications (P = 0.5164). There was a trend that the postoperative complications increased with the deterioration of pulmonary function. The correlation between postoperative pulmonary complications and the surgical approach was statistically significant (P = 0.0000); the incidence of postoperative pulmonary complication of transthoracic procedure was 18 times as that of posterior approach. No significant difference was noted regarding ages, preoperative coronal Cobb angles, and preoperative pulmonary function between these 2 groups. There was no significant correlation between preoperative pulmonary symptoms and postoperative complications. CONCLUSIONS: The incidence of postoperative pulmonary complications increased with the deterioration of pulmonary function tests. The posterior procedure had a very low incidence of postoperative pulmonary complications, but a transthoracic procedure increased the complications significantly. Preoperative pulmonary symptoms usually predicted abnormal results of pulmonary function tests but had no correlation with postoperative pulmonary complication.

Adolescent↗

Pulmonary function changes following surgical correction for pectus excavatum.

OBJECTIVE: To assess whether and to what extent pulmonary function returns to normal after surgical correction for pectus excavatum. METHODS: Twenty-seven patients who could be examined in person at the outpatient department of our hospital were included in this study. Of these patients, 24 were boys and 3 were girls, with age ranging from 3 to 16 years (mean: 8.67 years). The mean age at surgery was 4 years and mean years at follow-up was 6.8. Pulmonary function measurements included inspiratory vital capacity (IVC), total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC), RV/TLC ratio, maximal voluntary ventilation (MVV), forced ventilatory capacity (FVC), forced expiratory volume in one second (FEV1), maximal mid-expiratory flow (MMEF), maximal expiratory flow at 75% vital capacity (V75), maximal expiratory flow at 50% vital capacity (V50), maximal expiratory flow at 25% vital capacity (V25) and breathing reserve ratio (BR). RESULTS: TLC, FRC, MVV, MMEF, V75 and V50 were not different from normal values. IVC, FVC, FEV1 and V25 were significantly decreased compared with normal values. RV and RV/TLC were high in 87.5% cases. CONCLUSIONS: Preoperative symptoms improved substantially after operation. Little airway obstruction was observed postoperatively, suggesting that patients with pectus excavatum should have surgery as early in life as possible, preferably by age 3.

Adolescent↗

Clinical correlates of an elevated diffusing capacity for carbon monoxide corrected for alveolar volume.

The diffusing capacity for carbon monoxide is partially dependent on lung volume at which it is measured. As a consequence, the diffusing capacity for carbon monoxide is often indexed to the simultaneously measured lung volume (VA), giving rise to the term DL/VA. This reflects the diffusing capacity of carbon monoxide per unit area of lung parenchyma. The authors investigated the pulmonary function of 18 patients who had an elevated DL/VA in order to identify factors that could account for this abnormality. Sixteen of the 18 had a reduction in vital capacity. The vital capacity was reduced because of obesity, pleural disease, and diaphragmatic dysfunction. Eight of nine patients with a body mass index > 30 kg/m2 had a reduction in vital capacity. On the basis of these findings, we believe that an elevated DL/VA should alert the physician to the possibility of 1) an increase in pulmonary capillary blood volume (Vc) (obesity, polycythemia, negative pleural pressure), and 2) reduced VA that does not directly affect the pulmonary capillary bed (pleural disease, neuromuscular disease).

Adult↗

Treatment of respiratory insufficiency in Duchenne's muscular dystrophy: nasal ventilation in the initial stages.

Fourteen patients with Duchenne's muscular dystrophy (DMD) received nasal ventilation at the beginning of the declining phase of their vital capacity (VC). At that point, the mean value (SD) of their vital capacity was 1,756 (363) mL notably inferior to the predicted values. Nasal ventilation was performed according to a precise protocol, with an average nocturnal duration of 8 h. The annual decline of vital capacity was about 70 ml, showing a significant reduction compared with the value of 200 mL.yr-1 of untreated patients. Follow-up of treated patients (3.8 yrs; SD 1.9 yrs) has enabled us to distinguish different groups of results with useful practical consequences. In 29% of cases, the initial progression of decline of vital capacity was poorly modified by the treatment. In 71% of patients, the decline of VC was significantly decreased. In 35% of cases tracheal ventilation followed nasal ventilation. The normal mortality rate of DMD has greatly changed as a result of this method.

Adolescent↗

Lung function and risk of myocardial infarction and sudden cardiac death.

In a serach for risk factors for myocardial infarction and sudden cardiac death, the mean total vital capacity as measured at multiphasic health checkups was lower in persons who later had a first myocardial infarction than in risk-factor-matched controls (3.17 vs. 3.29 liters, 395 pairs, P less than 0.05) and non-risk-factor-matched controls (3.16 vs. 3.41 liters, 401 pairs, P less than 0.001). Findings were little affected by age and height adjustment and were similar for sudden cardiac death. The first-second vital capacity was also inversely related to later development of these conditions, but the ratio of that measurement to total vital capacity was not. Heavy smoking, productive cough, exertional dyspnea and cardiac enlargement were associated with diminished total capacity. However, exclusion of subjects with these findings did not reduce the predictive value of total vital capacity. Diminished vital capacity deserves continued attention as a possible coronary risk factor. Its relation to subsequent coronary events is not well explained.

Adult↗