Stable Clinical State Research Articles

Relationship of Sputum Color to Nature and Outpatient Management of Acute Exacerbations of COPD

To stratify COPD patients presenting with an acute exacerbation on the basis of sputum color and to relate this to the isolation and viable numbers of bacteria recovered on culture. Open, longitudinal study of sputum characteristics and acute-phase proteins. Patients presenting to primary-care physicians in the United Kingdom. Patients were followed up as outpatients in specialist clinic. One hundred twenty-one patients with acute exacerbations of COPD were assessed together with a single sputum sample on the day of presentation (89 of whom produced a satisfactory sputum sample for analysis). One hundred nine patients were assessed 2 months later when they had returned to their stable clinical state. The expectoration of green, purulent sputum was taken as the primary indication for antibiotic therapy, whereas white or clear sputum was not considered representative of a bacterial episode and the need for antibiotic therapy. A positive bacterial culture was obtained from 84% of patients sputum if it was purulent on presentation compared with only 38% if it was mucoid (p < 0.0001). When restudied in the stable clinical state, the incidence of a positive bacterial culture was similar for both groups (38% and 41%, respectively). C-reactive protein concentrations were significantly raised (p < 0.0001) if the sputum was purulent (median, 4.5 mg/L; interquartile range [IQR], 6. 2 to 35.8). In the stable clinical state, sputum color improved significantly in the group who presented with purulent sputum from a median color number of 4.0 (IQR, 4.0 to 5.0) to 3.0 (IQR, 2.0 to 4. 0; p < 0.0001), and this was associated with a fall in median C-reactive protein level to 2.7 mg/L (IQR, 1.0 to 6.6; p < 0.0001). The presence of green (purulent) sputum was 94.4% sensitive and 77.0% specific for the yield of a high bacterial load and indicates a clear subset of patient episodes identified at presentation that is likely to benefit most from antibiotic therapy. All patients who produced white (mucoid) sputum during the acute exacerbation improved without antibiotic therapy, and sputum characteristics remained the same even when the patients had returned to their stable clinical state.

Bronchial Inflammation: Its Relationship to Colonizing Microbial Load and α1-Antitrypsin Deficiency

Neutrophil elastase is capable of generating many of the features of chronic bronchial disease. In patients with COPD, airways inflammation with neutrophil recruitment and elastase release is positively correlated with colonizing bacterial load in the stable clinical state (p < 0.0005). In addition, alpha(1)-antitrypsin deficiency is associated with a greater neutrophil load, higher elastase activity, leukotriene-B(4) concentration, and serum protein leak than matched patients without deficiency (p < 0.005). These data confirm an effect of bronchial colonization on airways inflammation in COPD and indicate the role of alpha(1)-antitrypsin in its modulation.

Measuring quality of life in children with rhinoconjunctivitis

Objective: The objective of this study was to develop, pretest, and validate a questionnaire to measure quality of life in children with seasonal allergic rhinoconjunctivitis (SAR). Methods (development study): Thirty-four children with SAR were enrolled from summer camps, notices in the media, and an allergy clinic (Southern Ontario). After generating a pool of 48 potentially important quality of life items, the children identified the ones that they experienced with their SAR and scored each for bother (1 = a little bothered to 4 = extremely bothered). Items identified most frequently and with the highest bother score were included in the Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ). The PRQLQ was pretested for ease completion and accuracy of understanding. Results (development study): The PRQLQ has 23 items in five domains (nose symptoms, eye symptoms, practical problems, other symptoms, and activities). Responses are given on a seven-point scale, and children are asked to score their experiences during the previous 7 days. Methods (validation study): Seventy-five children with symptomatic SAR were enrolled from notices in the media and a pediatric allergy clinic (Austin, Tex.). A single cohort design was used, with children assessed at 0, 1, and 3 weeks. The PRQLQ was administered to the children by a trained interviewer at 1 and 3 weeks. A conventional nasal symptom daily diary was completed for 1 week before each of these clinic visits. Global ratings were completed at the final visit. Results (validation study): In patients who were stable between clinic visits, the PRQLQ demonstrated good reliability (intraclass correlation coefficient = 0.93). The questionnaire was very responsive to change ( p < 0.001) and was able to differentiate between patients who were in a stable clinical state and those whose clinical state changed between visits ( p = 0.005). Correlations between the PRQLQ and diary scores were close to predicted and supported both the cross-sectional and longitudinal validity of the PRQLQ. Conclusions: The PRQLQ measures the quality of life impairments important to children with SAR. Children provide reliable and accurate responses, the measurement properties are strong, and the questionnaire can be used with confidence in clinical trials, clinical practice, and surveys. (J Allergy Clin Immunol 1998;101:163-70.)

Effect of smoking on neuroleptics in schizophrenia

The effect of smoking on daily doses and plasma levels of neuroleptics prescribed for schizophrenic patients was studied. 90 outpatients with schizophrenic disorder (DSM-III-R) who were on a stable regimen of psychotropic medication and showed a stable clinical state were included in a double-blind placebo-controlled trial. Data were collected and blood tests taken at the baseline interview. The plasma levels were obtained for 52 patients. Daily neuroleptic doses converted to chlorpromazine equivalents correlated significantly (r = 0.436) with the plasma levels of their unmetabolised fractions. The neuroleptic doses increased with age in smokers, while in nonsmokers they decreased. Neither sex, age nor smoking had a significant association with the neuroleptic plasma levels. Smoking seems to lead to increased neuroleptic dosages in postmenopausal schizophrenics by increasing hepatic metabolism and renal excretion of the drugs and possibly enhancing dopamine release. It is also possible that older smoking patients form a selected group of heavy smoker and they, therefore, need exceptionally high neuroleptic doses.

Progression of coronary artery disease in non-dilated sites in the months following balloon angioplasty: time-dependent relation with restenosis.

There is scant information on the progression of coronary artery disease in non-dilated sites in the months following percutaneous transluminal coronary angioplasty (PTCA) or on its relationship with restenosis. To assess the incidence of this progression and its relationship with restenosis at various times after PTCA, the authors selected 371 consecutive patients who had undergone a first successful PTCA for angina on native coronaries followed by a repeat angiographic study. The angiograms were analysed by a computer-assisted method; progression was defined as a 20% decrease in diameter and restenosis as a 30% decrease in diameter or a return to > 50% stenosis. The relationship between progression and restenosis was analysed in the whole population and then, using the Mantel-Haenszel chi-square test, in two subgroups: patients with a stable clinical state, who were restudied routinely and those whose worsened state had prompted repeat angiography. The relationship was assessed at different times between angioplasty and the repeat angiography. Progression was observed in 80 patients (22%) and restenosis in 155 patients (42%). There was a highly significant relationship between progression and restenosis in the total population (chi 2 = 26.4, odds ratio = 3.9 and P < 0.0003) and in the group of patients that were routinely restudied (chi 2 = 31.6, odds ratio = 5.3 and P < 0.0001), but not in the group of patients in whom restudy was performed because of clinical worsening (chi 2 = 0.13, odds ratio = 1.5 and P = NS). With respect to the length of follow-up, in the total population the relationship was significant only at 6 and 7 months (P < 0.0001), and in the group receiving a routine restudy only at 4-5 and 6-7 months (P < 0.001). Progression in non-dilated sites appeared to be strongly and transiently linked with restenosis, suggesting that PTCA may enhance both restenosis and progression over a short period.

Diet-induced thermogenesis in chronic obstructive pulmonary disease.

Increased resting energy expenditure and malnutrition are frequently observed in patients with COPD. The aim of this study was to examine the possible contribution of an increased diet-induced thermogenesis (DIT) to weight loss. Eleven patients with COPD in stable clinical state and 11 healthy control subjects were studied. Resting energy expenditure (REE) was measured by standard methods of indirect calorimetry, using a ventilated canopy. Premeal REE was measured after an overnight fast. All subjects then received a balanced liquid test meal with a caloric content that was 0.3 times their REE extrapolated to 24 h. Diet-induced thermogenesis was measured over 130 min. Premeal REE was 109.9 +/- 11.7% of predicted values in the COPD group and 97.5 +/- 9.6% of predicted in the control group (p < 0.01). Seventy minutes after the test meal, REE had increased by 18.8 +/- 8.5% in the COPD group and by 15.1 +/- 5.8% in the control group (NS). After 130 min, REE had increased by 16.4 +/- 7.1% in the COPD group and by 12.4 +/- 5.3% in the control group (NS). The DIT expressed as a percentage of the caloric content of the meal was 4.3 +/- 1.6% in the COPD group and 3.3 +/- 1.4% in the control group (NS). We conclude that patients with stable COPD, although hypermetabolic at rest, do not show an increased DIT.

An Analysis of Sequential Physiologic Changes in Hypoxic Cor Pulmonale during Long-term Oxygen Therapy

Physiologic changes were studied retrospectively in 37 patients with hypoxic cor pulmonale who died during long-term oxygen therapy (LTOT). The subjects were assessed during periods of clinical stability for each year on LTOT. At the onset of treatment, their mean age (+/- SEM) was 60.0 +/- 1.3 years, and at the time of death, they were aged 65.0 +/- 1.3 years. The median duration of LTOT was five years. For each year leading up to death, mean values of FEV1, PaO2, and PaCO2 were obtained. A rate of decline of FEV1 of 73 +/- 10 ml/yr was observed, and this was accompanied by a decline in PaO2 of 0.47 +/- 0.01 kPa/yr. Patients died with a mean FEV1 of 0.55 +/- 0.04 L and a PaO2 of 5.1 +/- 0.2 kPa. A small rise in PaCO2 occurred, on average 0.25 +/- 0.09 kPa/yr, throughout the study, but accelerating in many cases during the three years before death. Hypoxic cor pulmonale appears to be associated with a rapid deterioration in airway function, a steady decline in PaO2, and a slow rise in PaCO2 during the years leading up to death. These physiologic changes measured in a stable clinical state while breathing air appear to occur in spite of LTOT. The LTOT may merely prevent death from episodes of severe hypoxemia while the pathophysiologic changes in the lung progress. Hence the benefit to be expected from LTOT is only temporary. Generally, those patients with lower levels of FEV1 will obtain diminishing clinical benefit, inversely related to the severity of airflow obstruction at the time of commencement of LTOT.

Energy expenditure and rib cage-abdominal motion in chronic obstructive pulmonary disease

The resting energy expenditure (REE) was measured by indirect calorimetry in 10 patients with chronic obstructive pulmonary disease (COPD) in stable clinical state and in 10 normal subjects. In order to avoid artefactually increased values, REE was obtained from prolonged measurements in steady state using a ventilated hood, without facial apparatus. The REE of COPD patients was significantly increased to 117% of predicted basal metabolic rate and to 125% of the control group values. Rib cage and abdominal movements were measured in COPD patients by inductance plethysmography and expressed with three indices: rib cage contribution to tidal volume (RC/VT), variability in compartmental contribution to tidal volume (SD RC/VT), and maximal compartmental amplitude/tidal volume ratio (MCA/VT). No correlation was found between REE and any of the indices of rib cage and abdominal motion. We conclude that the REE is increased in patients with COPD in stable clinical state, but is not related to the degree of abnormal rib cage-abdominal motion.

Increased resting energy expenditure in cystic fibrosis.

To explore the hypothesis that there is an increased metabolic rate in cystic fibrosis, resting energy expenditure was measured by indirect calorimetry in 23 subjects with cystic fibrosis in a stable clinical state and in 42 normal control subjects. Resting energy expenditure was found to be elevated by an average of 0.45 MJ/24 h [95% confidence interval (CI) = 0.26-0.64, t = 4.91, P less than 0.001] (108 kcal/24 h), or 9.2% above expected values derived from the regression relating resting energy expenditure to whole body weight and sex in control subjects. When related to lean body mass, values were still elevated by 0.36 MJ/24 h (95% CI = 0.18-0.53, t = 4.15, P less than 0.001) (86 kcal/24 h), or 7.2%. The increased values were found to be independent of age, sex, or body size. There were significant correlations between increased values and poor pulmonary function as measured by the ratio of the forced expiratory volume in 1 s to forced vital capacity (r = -0.44, P less than 0.05) and subclinical infection as indicated by the blood leukocyte count (r = 0.40, P less than 0.05). However, the correlations were low, suggesting that other factors may contribute to the increased resting energy expenditure, possibly including the putative metabolic defect in cystic fibrosis.

THE COURSE OF IMPROVEMENT IN FUNCTIONAL CAPACITY DURING CARDIAC REHABILITATION FOLLWING CARDIAC TRANSPLANTATION

Cardiac transplantation (CT) improves survival and functional capacity. The time course of improvement in functional capacity in severely debilitated patients following Cr is not known. This study was undertaken to define the time course of return to Functional Class I in a series of 6 patients who underwent CT for and-stage heart failure (3 ischemic and 3 idiopathic) and then entered a Cardiac Rehabilitation Program (CRP). Their mean age was 37 years (range 14 to 56). Four patients were Functional Class IV and 2 were Class III prior to surgery. Symptom limited exercise stress tests were performed at the time of discharge from the hospital (mean 5.5 weeks, range=2 - 13 weeks) and then aerially at about 7-week intervals during a stable clinical state without evidence of acute rejection or infection. Post-operative (implications did occur, including 11 episodes of rejection and 5 infections requiring treatment. All patients underwent a modified Phase I and II CRP. The results of the GXTs were: In spite of their severe pre-op disability and serious post-op complications, all patients reached Functional Class I within 17 weeks of discharge (X = 7.6 weeks). All patients were successful in returning to their pre-morbid status as well (ie. work, school etc.). These findings, in this diverse group of unselected patients, indicate that CT followed by CRP can return patients to active productive lifestyles in a reasonable period of time

Three-month follow-up of arterial blood gas determinations in candidates for long-term oxygen therapy. A multicentric study.

One hundred seventeen patients with severe chronic obstructive pulmonary disease whose PaO2 in a stable clinical state ranged from 41 to 59 mmHg, were included in a multicentric controlled study on the effects of long-term O2 therapy (LTO), and the results of the 3-month probationary period are given here. Arterial blood gases were checked every month in order to assess the stability of hypoxemia. Time 0 represented the beginning and T3 the end of the probationary period. Patients whose PaO2 at T3 was still between 41 and 59 mmHg could be accepted for the long-term study (Group A), whereas patients whose PaO2 had increased over 59 mmHg were excluded (Group B). Only 77 patients could be followed up regularly from T0 to T3 (40 patients were lost to follow-up, missed some visits, or suffered from acute exacerbations of the disease) and 23 of them had a PaO2 at T3 that exceeded 59 mmHg (Group B), allowing the inclusion of 54 patients (Group A) in the long-term study. Patients in Groups A and B did not differ with regard to pulmonary volumes, PaCO2 at T0 or a past history of right heart failure. Arterial O2 tension at T0 was slightly and significantly (p less than 0.02) lower in Group A (51.3 +/- 5.5 mmHg) than in Group B (54.5 +/- 3.8 mmHg), but there was an important overlapping of individual results from one group to another.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of antibiotic treatment on sputum elastase in bronchiectatic outpatients in a stable clinical state.

Broad spectrum antibiotic treatment was given on 21 occasions to 15 patients with bronchiectasis who regularly produced purulent, elastase positive secretions. Although the results showed that sputum clearing--that is, changing from purulent to mucoid--largely depended on the pathogenic organism isolated, this was not exclusively the case and in some cases sputum growing sensitive organisms failed to clear whereas clearing occurred in other samples containing resistant organisms or no obvious pathogens. Clearing of sputum was achieved eventually in 12 of the patients and this was associated with the disappearance of elastase activity, although it returned in 10 patients within one week of stopping treatment. There was no change in sputum elastase where the sputum failed to clear. The clearance of elastase activity was associated with a decrease in protein transudation into the lung secretions. The sputum:serum albumin concentration ratio fell (p less than 0.005) from a mean (SD) of 2.32 (1.56) X 10(-2) in these 12 patients before treatment to 1.09 (0.40) X 10(-2) within the first week of treatment, but rose again to 2.07 (1.29) X 10(-2) within one week of stopping treatment. The results suggest that antibiotic treatment when patients are in a stable state may have a beneficial effect on the pathogenic nature of lung secretions and inflammation within the lung.

The "on-off" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport.

To determine whether the oscillating clinical response to levodopa in Parkinson's disease (the "on-off" phenomenon) reflects fluctuations in absorption and transport of the drug, we investigated this phenomenon in nine patients with an oscillating motor state. We studied the response to continuous infusion of levodopa and the effects of meals on the plasma levodopa concentrations and on the clinical response during oral and intravenous administration of the drug. Meals reduced peak plasma levodopa concentrations by 29 per cent and delayed absorption by 34 minutes. Bypassing absorption by constant infusion of the drug produced a stable clinical state lasting for 12 hours in all of six patients and for up to 36 hours in some. High-protein meals or oral phenylalanine, leucine, or isoleucine (100 mg per kilogram of body weight) reversed the therapeutic effect of infused levodopa without reducing plasma levodopa concentrations. Glycine and lysine at identical doses had no effect. We conclude that interference with absorption of levodopa by food and by competition between large neutral amino acids and levodopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson's disease.

The role of computed tomography in the evaluation of blunt abdominal trauma in children

Computed tomography was used in the evaluation and follow-up of blunt intra-abdominal injuries in 46 children. The use of this modality resulted in a rapid and accurate diagnosis in the patients studied. Indications for CT scan examination included: a stable clinical state, symptoms and signs suggestive of intra-abdominal injury, hypotension responding to minimal fluid resuscitation, slowly declining hematocrit, hematuria, or suspicious radiographs. Patients with unstable vital signs were not considered candidates for CT scanning. The value of the protocol and CT scanning procedure itself was evident by the high yield of positive results (74% of the patients studied). Of the 12 children with urologic trauma, 2 had severe renal injuries that were not suspected by infusion i.v. pyelography and in one instance by arteriography. The magnitude and extent of perirenal hemorrhage was easily demonstrated. Thirteen patients had splenic lacerations, while 7 children had suspected hepatic injuries all accurately demonstrated by CT scans. Intra-peritoneal blood was easily detected. Two patients had pancreaticoduodenal injuries. Eleven of 12 renal injuries, 9 of 13 splenic lacerations, 5 of 7 hepatic injuries, and both pancreaticoduodenal injuries were successfully treated nonoperatively. The appropriateness of conservative management was substantiated by periodic follow-up examinations. This study demonstrated the improved sensitivity of CT scanning and ability to visualize intra- and retroperitoneal structures simultaneously when compared to more conventional methods of radiographic evaluation. The applications of CT scanning in the evaluation of the traumatized patient reduces the number of ancillary tests required for diagnosis, provides more accurate information regarding the extent and severity of the injury, and results in more appropriate decisions regarding the need for exploration versus nonoperative management. In addition, this modality offers an accurate method for long-term follow-up, allowing definitive recommendations concerning activities. Computed tomography was used in the evaluation and follow-up of blunt intra-abdominal injuries in 46 children. The use of this modality resulted in a rapid and accurate diagnosis in the patients studied. Indications for CT scan examination included: a stable clinical state, symptoms and signs suggestive of intra-abdominal injury, hypotension responding to minimal fluid resuscitation, slowly declining hematocrit, hematuria, or suspicious radiographs. Patients with unstable vital signs were not considered candidates for CT scanning. The value of the protocol and CT scanning procedure itself was evident by the high yield of positive results (74% of the patients studied). Of the 12 children with urologic trauma, 2 had severe renal injuries that were not suspected by infusion i.v. pyelography and in one instance by arteriography. The magnitude and extent of perirenal hemorrhage was easily demonstrated. Thirteen patients had splenic lacerations, while 7 children had suspected hepatic injuries all accurately demonstrated by CT scans. Intra-peritoneal blood was easily detected. Two patients had pancreaticoduodenal injuries. Eleven of 12 renal injuries, 9 of 13 splenic lacerations, 5 of 7 hepatic injuries, and both pancreaticoduodenal injuries were successfully treated nonoperatively. The appropriateness of conservative management was substantiated by periodic follow-up examinations. This study demonstrated the improved sensitivity of CT scanning and ability to visualize intra- and retroperitoneal structures simultaneously when compared to more conventional methods of radiographic evaluation. The applications of CT scanning in the evaluation of the traumatized patient reduces the number of ancillary tests required for diagnosis, provides more accurate information regarding the extent and severity of the injury, and results in more appropriate decisions regarding the need for exploration versus nonoperative management. In addition, this modality offers an accurate method for long-term follow-up, allowing definitive recommendations concerning activities.

A study of plasma proteins in the sol phase of sputum from patients with chronic bronchitis.

We have studied the sputum/serum protein concentration ratios from 23 patients with bronchitis both in the stable clinical state and during acute chest infections. During the stable state there was a significant negative correlation (2 P less than 0.005) between the ratio and protein size. The ratios of IgG, IgA, C3, and alpha 1-antichymotrypsin were significantly displaced from this relation suggesting local production in the lung. IgM was found in all samples and alpha 2-macroglobulin in 55% of non-infected samples which may be the result of local production rather than transudation from serum, because of their larger size. During acute chest infections the albumin content of sputum rose from a mean sputum/serum ratio of 0.83 (SE +/- 0.08) X 10(-2) to 13.77 (SE +/- 3.21 X 10(-2) suggesting increased transudation from the blood. In the presence of increased transudation, local production of protein appears to be less significant.

Bronchodilator and corticosteroid effects on regional and total airway resistance in patients with asthma, chronic bronchitis, and chronic pulmonary emphysema.

Regional ventilation of 6 lung zones and total airway resistance were measured before and after inhalation of a bronchodilator in 8 normal subjects, 10 patients with bronchial asthma, and 11 patients with chronic bronchitis and/or chronic pulmonary emphysema. In addition, 3 patients with asthma and one with emphysema were studied by the same methods before and after the oral administration of 60 mg of prednisone per day for 2 weeks. The patients were in a relatively stable clinical state when studied. Airway resistance and thoracic gas volume were measured in a body plethysmograph, and specific airway conductance was calculated. Regional ventilation was measured by a washout technique using radioactive xenon. Because breathing frequency and tidal volume were approximately the same in the before and after bronchodilator studies of regional ventilation, changes in the latter probably reflected changes in regional airway resistance rather than regional pulmonary compliance. Five of 10 patients with asthma an...