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A factor analysis of dyspnea ratings, respiratory muscle strength, and lung function in patients with chronic obstructive pulmonary disease.

The purpose of this study was to demonstrate that clinical ratings of dyspnea and physiologic function are separate dimensions underlying the pathophysiology of chronic obstructive pulmonary disease (COPD). We used principal-components factor analysis to confirm these dimensions using data collected prospectively in 86 symptomatic patients with COPD. Three different instruments were used to rate dyspnea: a modified Medical Research Council (MRC) scale, the oxygen cost diagram (OCD), and the baseline dyspnea index (BDI). Measures of physiologic function included standard spirometric measures (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) and maximal inspiratory (PImax) and expiratory (PEmax) mouth pressures. Age of the 65 male and 21 female subjects was 62.9 +/- 1.2 yr (mean +/- SEM). All three clinical scales were significantly correlated with physiologic function (range of r values, 0.32 to 0.45; p less than 0.05), except for the relationship between the MRC scale and PEmax (r = -0.14; p = NS). The factor analysis yielded three factors that accounted for 71.9% of the total variance of the data: clinical ratings of dyspnea (MRC scale, OCD, and BDI) loaded on the first factor; maximal respiratory pressures and gender loaded on the second factor; and lung function and age loaded on the third factor. Additional post hoc factor analysis provided similar results when the sample was divided into two subgroups by randomization, by severity of dyspnea ratings, or by severity of airflow obstruction. We conclude that dyspnea ratings, maximal respiratory pressures, and lung function are separate factors or quantities that independently characterize the condition of patients with COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea↗

Observations on Maori-European lung function differences.

One hundred and twenty-one regular soldiers between the ages of 18 and 34 years, who had lived and worked under identical conditions for the two previous years were examined. All subjects with respiratory symptoms of wheeze, dyspnoea, persistent cough or sputum were excluded. Smoking, per se, was not a reason for exclusion. Eighty-three "respiratorily fit" men, comprising 47 Maoris and 36 Europeans, were studied to see whether height, weight or obesity could account for the ethnic differences in lung function. The forced vital capacity in the Maoris was found to be about 9% lower than in the Europeans. The one-second forced expiratory volume of the Maoris was about 8% lower than in the Europeans. No significant difference could be found in the peak expiratory flow rates between the two ethnic groups. The only significant physical difference found between the two ethnic groups was that the Maoris were heavier for their height than the Europeans. Statistical tests showed that neither weight nor an obesity index accounted for the ethnic differences in lung function. Full laboratory investigation of these ethnic differences is recommended.

Adolescent↗

The relationship between health-related quality of life, lung function and daily symptoms in patients with persistent asthma.

It is generally believed that there is a direct correlation between asthma control and a patient's health-related quality of life (HRQL). Objective and subjective measures of asthma control are used interchangeably. A retrospective analysis from 8994 patients from 27 randomized, controlled clinical trials with persistent asthma was conducted to determine the degree of association which exists between objective (lung function) and subjective (symptoms, quality of life) measures. Assessments were made via forced expiratory volume in 1-second (FEV1), self-reported symptoms and the Asthma Quality of Life Questionnaire (AQLQ) overall scores. Baseline percent predicted FEV1 was weakly correlated with baseline symptom-free days (SFD) and baseline overall AQLQ scores (r=0.11 and 0.09, respectively; P <0.001). Changes in percent predicted FEV1 correlated weakly with changes in SFD but was more strongly correlated with changes in overall AQLQ scores (r= 0.26 and 0.38, respectively; P <0.001). Additionally, SFD at both baseline and endpoint were moderately correlated with overall AQLQ scores at baseline and endpoint (r=0.36 and 0.44; P <0.001). This study suggests that the impact of asthma on a patients' HRQL is not fully accounted for by objective measures such as lung function. Thus, HRQL data complements rather than duplicates results from traditional, objective assessments of asthma control.

Adolescent↗

Lung function and bacterial proliferation in experimental neonatal pneumonia in ventilated rabbits exposed to monoclonal antibody to surfactant protein A.

Surfactant protein A (SP-A) increases the resistance of surfactant to inhibition by plasma and other proteins. In a previous study we found that a monoclonal anti-SP-A antibody (R 5) increased the sensitivity of surfactant to inhibition by fibrinogen in vivo and in vitro. SP-A has been shown to stimulate microbial phagocytosis and killing by alveolar macrophages. We hypothesized that using R 5 to inactivate SP-A in an animal model mimicking congenital group B streptococcal (GBS) pneumonia might result in increased bacterial proliferation and a deterioration in lung function. Newborn near term rabbits were delivered by Cesarean section, anesthetized, tracheotomized, and ventilated for 5 h in a plethysmograph system allowing measurement of dynamic lung-thorax compliance. Postnatally the animals received one intratracheal injection (5 ml/kg) of R 5, nonspecific IgG, or normal saline. At 30 min all animals received a standard dose of an encapsulated GBS strain by intratracheal injection. The number of bacteria (mean log10 CFU/g lung +/- S.D.; CFU = colony forming unit) was evaluated in lung homogenates. Histologic lung sections were judged by light microscopy. Bacterial proliferation was similar in rabbits treated with the monoclonal antibody (9.33 +/- 0.39; n = 14) and in control animals receiving saline (9.16 +/- 0.35; n = 14) or nonspecific IgG (9.26 +/- 0.31; n = 11). No significant differences were noted on the histologic analysis or in measurements of lung function. We conclude that intratracheal instillation of a monoclonal anti-SP-A antibody did not increase bacterial proliferation in GBS-infected newborn rabbits. These findings suggest that SP-A does not play an important role in protection against encapsulated GBS strains in the neonatal period.

Animals↗

Lung function and surface electromyography of intercostal muscles in cement mill workers.

Impairment of pulmonary function in cement mill workers has been previously reported without considering a variety of parameters that can help evaluate more thoroughly the effect of cement dust on the respiratory system. In addition, an integrated approach has not been considered to assert the involvement of respiratory muscles. Therefore, in the present study spirometry and surface electromyography (SEMG) of intercostal muscles were used for indicating pulmonary impairment. In this study, a group of 50, apparently healthy volunteers, male cement mill workers aged 20-60 years with exposure of 13 years on average, were randomly selected. They were matched with another group of 50 control healthy male subjects in terms of age, height, weight and socioeconomic status. Both groups met the standard exclusion criteria. Spirometry was performed on an electronic spirometer, while SEMG of intercostal muscles was performed by using a chart recorder. The results demonstrated statistically significant reduction in lung function parameters i.e., force vital capacity (FVC) (p < 0.0005); force expiratory volume in first second (FEV1) (p < 0.0005); peak expiratory flow (PEF) (p < 0.005); and maximum voluntary ventilation (MVV) (p < 0.0005) in cement mill workers, when compared with controls. However, the FEV1/FVC ratio was significantly higher (p < 0.025) in cement mill workers. Similarly, the parameters obtained from SEMG of intercostal muscles, i.e. number of peaks (NOP) (p < 0.0005); maximum peak amplitude (MPA) (p < 0.0005); peak to peak amplitude (PPA) (p < 0.0005); duration of response (DOR) (p < 0.0005) and maximum peak duration (MPD) (p < 0.0005), were significantly lower in cement mill workers than in controls. It is concluded that exposure to cement dust not only impairs lung function but also affects costal muscle performance, thus possibly indicating the decreased lung and thoracic compliance.

Adult↗

Effect of lycopene supplementation on lung function after exercise in young athletes who complain of exercise-induced bronchoconstriction symptoms.

BACKGROUND: It has been suggested that exercise-induced bronchoconstriction may involve oxidative stress. Strenuous exercise promotes free radical production, which can lead to many of the pathophysiologic changes associated with asthma, including bronchoconstriction, mucus secretion, and microvascular leakage. Lycopene has been shown to have high antioxidative activity. OBJECTIVE: To evaluate the effect of lycopene supplementation on airway hyperreactivity and inflammation in young athletes who complain of difficulty in breathing related to physical exertion. METHODS: Nineteen young athletes with exercise-related difficulty in breathing visited the exercise laboratory 3 times. During the first visit, participants underwent a baseline evaluation of exercise-induced bronchoconstriction. Daily for 1 week before each of the 2 subsequent visits, participants ingested 30 mg of lycopene (a natural antioxidant) or placebo (in randomized order, double-blind). A 2-week washout period was given between each visit. During each visit, lung functions were evaluated before and after an 8-minute run on the treadmill (85% of the predicted maximal heart rate). RESULTS: There was no difference in the mean+/-SD decrease in forced expiratory volume in 1 second after exercise during lycopene treatment compared with placebo treatment (11.8%+/-12.5% and 11.0%+/-11.6%). In addition, there was no apparent division into responders and nonresponders. CONCLUSION: A daily dose of lycopene for 1 week does not affect lung function after exercise and may not provide any protective effect against clinical difficulty in breathing in young athletes.

Adolescent↗

High levels of complement-activation capacity in sera from patients with cystic fibrosis correlate with high levels of IgG3 antibodies to Pseudomonas aeruginosa antigens and poor lung function.

Heat-stable opsonins from sera of cystic fibrosis (CF) patients were investigated for their ability to activate complement. Complement activation by Pseudomonas aeruginosa after opsonization with patient serum was examined in a complement-consumption assay. Absorption of patients' sera with formalin-treated and boiled bacteria removed specific antibodies and the complement activation decreased. We found a positive correlation between serum complement-activation ability and IgG3 antibody levels to lipopolysaccharide (LPS), alginate, and a crude mixture of P. aeruginosa antigens (sonicate) in a group of patients with high levels of anti-Pseudomonas precipitins. In the same group of patients a significant negative correlation was found between complement activation and lung function. Eighteen patients have been followed longitudinally with serum samples covering the pre-infection, the early, and the late stages of chronic infection. Patients with poor lung function showed significantly higher levels of complement-activation capacity. We conclude that patients with high levels of specific IgG3 antibodies are able to induce a high level of complement activation and then develop more aggressive pulmonary tissue damage, probably secondary to local immune complex formation.

Adolescent↗

Effect of internal thoracic artery preparation on blood loss, lung function, and pain.

BACKGROUND: Postoperative blood loss, respiratory distress, and pain after coronary artery operation were assessed in a prospective, randomized, clinical study comparing two techniques of internal thoracic artery preparation. METHODS: In group A (n = 57) the internal thoracic artery was dissected with the entire surrounding connective tissue after opening the pleura, using routine lateral pleural drainage. In group B (n = 55) a venoarterial pedicle was prepared without surrounding muscle leaving the pleura intact. We assessed blood loss, clinical outcome, lung function, location, intensity, and quality of pain 6 days and 3 months after the operation. RESULTS: Significantly higher blood loss was observed in group A (A, 608+/-58 mL; B, 470+/-48 mL; p = 0.027). Forced expiratory volume in 1 second was significantly decreased in group A 6 days after surgery (A, 76.0%+/-1.6%; B, 83.2%+/-1.6%; p = 0.020). The forced expiratory volume in 1 second correlated to inspiratory vital capacity, which confirmed the advantage of the venoarterial technique (A, 0.771+/-0.021; B, 0.832+/-0.020; p = 0.003). Vital capacity was significantly higher in the venoarterial group at 3 months (A, 85.2%+/-2.1%; B, 98.5%+/-1.2%; p = 0.009), but not on postoperative day 6. The incidence of pleural effusion and atelectasis was significantly higher in group A (effusion: A, 52.6%; B, 23.6%; p = 0.002; atelectasis: A, 42.1%; B, 20.0%, p = 0.015). Sternal pain (A, 36.8%; B, 9.1%; p = 0.001) and suspenders pain (A, 33.3%; B, 7.3%; p = 0.001) occurred more often in group A. When using a multidimensional pain score, patients in group A experienced significantly sharper (6 days: A, 6.7+/-0.3; B, 3.3+/-0.2; p = 0.018; 3 months: A, 3.5+/-0.3; B, 1.4+/-0.3; p = 0.046) and more annoying pain (6 days: A, 7.6+/-0.2; B, 2.7+/-0.1; p = 0.036; 3 months: A, 6.6+/-0.3; B, 2.3+/-0.2; p = 0.040). CONCLUSIONS: These results demonstrate that the venoarterial preparation technique is superior to conventional internal thoracic artery preparation regarding postoperative blood loss, lung function, and pain.

Female↗

Lung function in children and adolescents with antecedents of acute rheumatic fever.

Static lung volumes, CO-lung transfer, airway resistance, maximal expiratory flows and lung elastic properties were studied in 29 children and adolescents 1-10 years after recovery from acute rheumatic fever. There were essentially no changes in lung function even in the subjects with a residual valvular disease. The only abnormality was a tendency for the elastic lung recoil at TLC to be low, which is interpreted as probably reflecting a decrease in inspiratory muscle force.

Acute Disease↗

Diabetes mellitus, plasma glucose and lung function in a cross-sectional population study.

To assess possible associations between diabetes mellitus (DM), plasma glucose, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), we analysed the results from a cross-sectional study of 11,763 subjects. The subjects were 20 yrs of age or older and were representative of the population of Copenhagen City. Two hundred and eighty four of the participants had DM as assessed by questionnaire. One hundred and seven subjects who did not report having DM had a plasma concentration of glucose higher than or equal to 11.1 mmol.l-1. In all age groups of diabetic subjects there was a slight impairment of lung function. It was more prominent in diabetic subjects treated with insulin than in subjects treated with oral hypoglycaemic agents and/or diet. Even in subjects without known DM, there was a significant association between reduction in lung function and raised plasma glucose concentration. On average, FVC (and FEV1) was reduced by 334 ml (and 239 ml) in diabetic subjects treated with insulin, and by 184 ml (and 117 ml) in diabetic subjects treated with hypoglycaemic agents and/or diet compared to control subjects.

Adult↗

Feasibility and variability of neonatal and infant lung function measurement using the single occlusion technique.

INTRODUCTION: For possible use as a predictor of wheezing illnesses in routine care, we evaluated the feasibility and variability of measurement of passive respiratory mechanics in a large, open population of healthy neonates and infants. METHODS: As part of the ongoing Wheezing Illnesses Study Leidsche Rijn, respiratory compliance (Crs), respiratory resistance (Rrs), and time constant (taurs) were measured during natural sleep in 450 healthy term neonates and infants using the single-occlusion technique (SOT). Interobserver and intraobserver variability of data sampling and the subsequent selection and analysis of occlusions as well as intra-measurement variability were examined. RESULTS: Technically acceptable lung function measurements could be performed in 328 infants (73%). Low intraobserver and interobserver variability was found for both data sampling (intraclass correlation coefficient [ICC] > or = 0.87) and for selection and analysis of occlusions (ICC > or = 0.99). Intra-measurement variability was low, with a mean intra-measurement coefficients of variation for Crs, Rrs, and taurs of 8.5%, 10.4%, and 15.4%, respectively. Averaging three or more occlusions resulted in stable values of Crs, Rrs, and taurs. CONCLUSION: Results of this study indicate that feasibility and variability of lung function testing using the SOT is acceptable for use in large populations of healthy neonates and infants in routine care.

Airway Resistance↗

Effect of cessation of short-term therapy with ipratropium bromide on lung function and airway responsiveness.

Regular exposure to antimuscarinic drugs would be expected to upregulate airway muscarinic receptors and could cause a transient increase in airways obstruction if treatment was stopped or omitted. We have examined peak expiratory flow rate (PEFR) during treatment and forced expiratory flow in one second (FEV1) and airway responsiveness to three constrictor agonists (as the provocative dose of agonist causing a 20% fall in FEV1, (PD20)) following cessation of regular inhaled ipratropium bromide, in 13 subjects with mild stable asthma. Subjects inhaled placebo and ipratropium bromide, 80 microg q.i.d. for 14 days in a cross-over fashion with a 1 week run-in/wash-out period before and after each treatment period. Subjects recorded symptom scores and PEFR throughout the study, and FEV1 and PD20 to histamine, methacholine and metabisulphite were measured before and after cessation of treatment. When compared to baseline, FEV1 was lower after cessation of ipratropium than after placebo, with a significant difference 30 h after the last dose (difference 190 mL; 95% confidence interval (95% CI) 310-70 mL; p<0.02). FEV1 measured 6-10 days later, did not differ significantly. PEFR was significantly lower after cessation of ipratropium than after placebo on Day 15 (19-37 h after the last dose) (mean difference 4.6%; 95% CI 1.6-7.5%; p<0.01) but not on Day 16. There were no significant changes in PD20 histamine, methacholine and metabisulphite, symptom scores or rescue bronchodilator use after cessation of treatment. Thus, transient bronchoconstriction was found around 30 h after cessation of regular therapy with inhaled ipratropium for 2 weeks. The mechanism is unclear, as no evidence of muscarinic receptor upregulation was found. Although the changes were small and unlikely to be important for most patients, the results of this study indicate that the timing of lung function measurements relative to the last dose of ipratropium is important when interpreting the course of lung function in long-term studies.

Administration, Inhalation↗

Effect of whooping cough in infancy on subsequent lung function and bronchial reactivity.

Thirty-six children younger than 1 yr of age hospitalized for whooping cough approximately 9 yr previously (cases) were compared with 36 control children of the same age and sex. Subjects were sampled from participants in an earlier large field study of the long-term sequelae of whooping cough. Respiratory symptoms were more common in cases, although the differences were not statistically significant. Cases were significantly more likely either to be atopic or to have a family history of wheezing illness. There were no significant differences between cases and control subjects in lung function indices derived from maximal expiratory flow volume loops or from single-breath nitrogen washout tests or in bronchial reactivity as judged by the histamine challenge PC20. The evidence from both the present and the earlier study indicates that whooping cough is unlikely to be a causal factor in later respiratory illnesses and symptoms and that no deficit in lung function can be detected in later childhood. The disease may, however, occur more frequently or be more easily recognized in children with environmental or constitutional factors that predispose to respiratory morbidity.

Asthma↗

Regional lung function: physiology and clinical applications.

The current status of tests of regional lung function has been reviewed from the physiological and clinical standpoint. Recent technical innovations include the use of single photon and positron emission computerized tomography (SPECT and PET). For PET work, neon-19 (t 1/2 17 sec) has been introduced as a ventilation tracer, and fluorine-18 deoxyglucose as a marker of glucose metabolism. Indium-111 labelled neutrophils have been studied. Physiological measurements of the distribution of blood flow and ventilation are concentrating on non-gravitational influences such as the pattern of force generation by the respiratory muscles and vasomotor tone. Ventilation and perfusion imaging of the lung with the gamma camera has established itself as an essential screening test for the diagnosis of pulmonary embolic disease. Inhalation of a radio-labelled aerosol of small particle size (1 micron) may be an acceptable substitute for a radioactive gas ventilation scan. Mucociliary clearance has been investigated with radionuclide techniques. Measurements of regional lung water have been replaced by tracers sensitive to alterations of epithelial (inhaled 99Tcm-DTPA) or endothelial (i.v. 113Inm-transferrin) permeability. New techniques using positron emission tomography, such as measurements of extravascular lung density, regional ventilation (19Ne) and regional glucose metabolism (18F-deoxyglucose) have been discussed briefly.

Humans↗

Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: a pilot study.

BACKGROUND: Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin. However, nebulized colistin can cause bronchoconstriction in CF patients. Therefore, in the progress of developing a dry powder formula, the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects. To investigate the side effects, a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF-patients. METHODS: Nine CF-patients chronically infected with P. aeruginosa participated in a double blind, randomized cross over study. On two visits to the outpatient clinic, patients were submitted to either nebulized colistin sulphate or colistin sulphomethate solution. Lung function tests were performed immediately before and 15 and 30 min after nebulization. RESULTS: Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate. A significant decrease in mean changes (SD) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3% (8.6%), -5.7% (7.3%) and -8.4% (7.5%) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate (P < 0.05). Seven patients were not able to complete the nebulization of colistin sulphate because of throat irritation and severe cough. CONCLUSION: Based on these results it was concluded that inhalation with nebulized colistin sulphate is not suitable for treatment of CF patients chronically infected with P. aeruginosa. Colistin sulphomethate is the drug of choice for pulmonary administration of colistin.

Administration, Inhalation↗

Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids.

Corticosteroids mediate a variety of immunological actions and are commonly utilized in the treatment of a wide range of diseases. Unfortunately, therapy with this class of medications is associated with a large proportion of non-responders and significant side effects. Inhaled corticosteroids are the most commonly used asthma controller therapy. However, asthmatic response to corticosteroids also varies widely between individuals. We investigated the genetic contribution to the variation in response to inhaled corticosteroid therapy in asthma. The association of longitudinal change in lung function and single nucleotide polymorphisms from candidate genes crucial to the biologic actions of corticosteroids were evaluated in three independent asthmatic clinical trial populations utilizing inhaled corticosteroids as the primary therapy in at least one treatment arm. Variation in one gene, corticotropin-releasing hormone receptor 1 (CRHR1) was consistently associated with enhanced response to therapy in each of our three populations. Individuals homozygous for the variants of interest manifested a doubling to quadrupling of the lung function response to corticosteroids compared with lack of the variants (P-values ranging from 0.006 to 0.025 for our three asthmatic populations). As the primary receptor mediating the release of adrenocorticotropic hormone, which regulates endogenous cortisol levels, CRHR1 plays a pivotal, pleiotropic role in steroid biology. These data indicate that genetic variants in CRHR1 have pharmacogenetic effects influencing asthmatic response to corticosteroids, provide a rationale for predicting therapeutic response in asthma and other corticosteroid-treated diseases, and suggests this gene pathway as a potential novel therapeutic target.

Administration, Inhalation↗

Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ.

Lung function, smoking, age and mortality data in 158 adult severe alpha 1-antitrypsin deficient, PiZZ individuals, followed from 1963 to 1982 were analyzed. Low initial FEV1 value was significantly associated with increased mortality (p less than 0.005). A 3 yr mortality rate of 40% was found in individuals whose initial FEV1 values were less than 30% of that predicted. In contrast, the corresponding 3-yr mortality among those whose initial FEV1 values were between 30 and 65% of that predicted was only 7%. Smokers were found to have significantly lower FEV1 levels (p = 0.008) and higher mortality (p less than 0.005) than non-smokers. The difference between current and ex-smokers in mortality and FEV1 level were not statistically significant (p = 0.9 and p greater than 0.25, respectively). Cross-sectional analysis of the initial FEV1 values indicated a significant decline (p less than 0.005) of FEV1 with increasing age. This decline was greater among smokers than non-smokers. Longitudinal analysis of FEV1 rates of decline in 80 cases with follow-up FEV1 measurements failed to detect any significant differences between smokers and non-smokers, but was performed late in the disease process. The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed.

Adolescent↗