Kinetics of lung clearance of 99mTc-DTPA in smoking patients with sarcoidosis compared to healthy smokers.

Investigation of lung clearance of 99mTc-labelled diethylene triamine penta-acetic acid (DTPA) in smoking sarcoid patients has been impeded by difficulties to differ between pathology of clearance kinetics caused by sarcoidosis and by smoking. This study explores the kinetics of lung clearance of 99mTc-DTPA in 15 current smokers with intrathoracic sarcoidosis. The results are compared with findings from 16 healthy smokers. Measurements of lung clearance over 180 min, i.e. longer than usual, revealed in II of the sarcoid patients a bi-exponential lung clearance course, which is pathologic. All healthy smokers also showed a bi-exponential lung clearance. In the analysis of the bi-exponential curve an initial fast, and a slow clearance component could be separated. The smokers with sarcoidosis had a significantly higher elimination rate of the slow component than the healthy smokers. Thus, analysis of the late part of the lung clearance curve may be rewarding in smoking sarcoid patients. The study shows that lung clearance of 99mTc-DTPA may be a method useful also in smoking patients with sarcoidosis.

One year follow-up of lung clearance of 99mTc-diethylene triamine penta-acetic acid and disease activity in sarcoidosis.

BACKGROUND AND AIM OF THE WORK: In interstitial lung disease lung clearance of 99mTc-diethylenetriaminepentaacetic acid (DTPA) reflects alterations in the alveolar capillary barrier. Our objective was to describe changes in lung clearance during one year in sarcoidosis, and to relate clearance to other data of lung function and disease activity. METHODS: Twenty-three newly diagnosed patients were studied with respect to lung DTPA clearance, spirometry, 67Ga scintigraphy and serum angiotensin converting enzyme (SACE). Lung mechanics and arterial PO2 at rest and exercise were studied in patients with radiological parenchymal changes. Six of these patients were prescribed peroral steroids. RESULTS: At inclusion lung DTPA clearance measured over 30 minutes was 53 +/- 16 minutes and at follow-up 59 +/- 20 minutes (p > 0.05). The number of pathological clearance curves at inclusion was 10 and at follow-up 6. In treated patients lung DTPA clearance improved as did lung 67Ga score and SACE. However, lung clearance did not correlate significantly with changes in lung function or other activity parameters. CONCLUSIONS: Lung DTPA clearance reflects lung function from an aspect different from that of other methods. It seems sensitive to pathology reversed by steroids and may, in some cases, help in the evaluation of disease activity.

[Shortages in Swedish tuberculosis care. Good results only in 71 percent of cases after 12-month treatment as shown in a current study]. / Det finns brister inom den svenska tuberkulosvården. Fullgott resultat efter tolv månader hos endast 71 procent visar aktuell studie.

During the period August 1994-December 1995 783 cases of active tuberculos (TB) were notified to the health authorities in Sweden. By means of questionnaires sent to the consulting physicians (92 per cent response rate) the treatment outcome was studied twelve months after the diagnosis. Out of 676 patients only 71 per cent were reported to have completed the treatment and be cured of TB. This indicates that there is room for improvement as regards monitoring patients, if necessary by Directly Observed Therapy (DOT), in order to make sure that prescribed treatment is adhered to.

[Policy program to minimize spread of infection. Prolonged cough may be a sign of tuberculosis]. / Policyprogram för minskad smittspridning. Långdragen hosta kan vara tuberkulos.

In a worldwide epidemiological perspective, Sweden is well favoured with an annual tuberculosis incidence of approximately six cases per 100,000 of the population. Neither the impact of the HIV pandemic nor the occurrence of multiresistant strains of Mycobacterium tuberculosis has yet become a major problem in the care of tuberculosis patients in Sweden. Only a few per cent of HIV patients have developed tuberculosis, and during the period, 1991-94, only one per cent of M. tuberculosis isolates in Sweden were resistant to such antimycobacterials as isoniazid and rifampicin. However, the epidemiological situation in the neighbouring Baltic states is a matter for concern. Bovine tuberculosis has been eradicated in Sweden, the last case having been diagnosed in 1978. Although the reported efficacy of BCG (bacillus Calmette-Guérin) tuberculosis vaccine varies according to the population studied, protective rates of 70-85 per cent have been reported for Sweden and other west European countries. Re-vaccination of tuberculin-negative individuals has not been shown to yield added protection. The aim of a national programme for protection against tuberculosis is to preserve our favourable epidemiological situation by early detection of new cases, effective contact tracing, and BCG vaccination of children in population groups at risk. The primary means of achieving this is the education of health care personnel to retain tuberculosis as a differential diagnosis. Moreover, national guidelines for contact tracing must be duly observed, and immigrants from high prevalence areas need to be screened for tuberculosis. Registration of all cases of tuberculosis should be maintained at regional and national levels, and follow-up must be meticulous until a successful outcome of treatment is accomplished. Recommendations for dealing with tuberculosis should be made available and duly implemented at all hospitals caring for tuberculosis patients, in order to avoid nosocomial transmission. Although BCG vaccination at birth was formerly general in Sweden, since 1975 only children considered to be at risk have been vaccinated. Thus, non-vaccinated young adults are now entering the health care sector as students or employees, and should be offered BCG vaccination. Moreover, the epidemiological situation both in Sweden and in neighbouring countries needs to be monitored carefully in order that recommendations concerning BCG vaccination and other preventive measures can be modified if necessary.

Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers.

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of 99mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of 99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P < 0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P < 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P < 0.01). Differences in kinetics of clearance of 99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.

Long-term evaluation of penicillamine or cyclofenil in systemic sclerosis. Results from a two-year randomized study.

In a two-year prospective therapeutic trial 13 patients with systemic sclerosis (SSc) were treated with penicillamine, 9 with cyclofenil, and 7 with neither. At entry skin involvement and esophageal, lung, heart, and kidney function did not differ significantly between the groups. Reevaluation after one and two years did not show any significant changes in skin, esophageal, heart, and kidney manifestations, while lung function had slightly improved in both drug-treatment groups. This study thus shows little overall effect of penicillamine and cyclofenil, although both drugs may arrest worsening of pulmonary dysfunction.

Lung mechanics and gas exchange in steroid treated pulmonary sarcoidosis. A seven year follow-up.

Fifteen patients with pulmonary sarcoidosis, representing the functionally most severely affected quartile of referred patients, were prescribed steroids during one year. During this period and after 7 years on average, measurements were made of lung volumes, the static elastic pressure/volume (PstL/V) curve and lung resistance (RL). Lung mechanics and arterial blood gases were studied at exercise. Within months static compliance (CstL) and the arterial partial pressure of oxygen improved along with radiography. A modest positive trend continued throughout the follow-up. The vital capacity followed CstL changes closer than did the total lung capacity, which remained low. Though CstL improved, transpulmonary pressure at maximal inspiration increased and the upper part of the PstL/V curve became flatter. RL remained moderately increased. The course of the physiologic findings may be explained by fairly stable parenchymal and peribronchial fibrosis after cessation of active inflammation, and by regress of reflex inhibition of inspiration. Thus most subjects showed modest improvement during and after treatment. The initial study of lung function provided important prognostic information. The study does not allow conclusive evidence with respect to long term benefit of treatment, but encourages continued use of steroids under the guidance of function tests.

Granulocytes and their secretory products, myeloperoxidase and eosinophil cationic protein, in bronchoalveolar lavage fluids from two lung lobes in normal subjects.

The interlobar variability of lavage neutrophils and eosinophils was studied in twelve healthy subjects. In addition, the interlobar variation of the neutrophil cell marker myeloperoxidase (MPO) and the eosinophil cell marker eosinophil cationic protein (ECP) was assessed. Bronchial washes (BW), as defined by the first aspirated lavage aliquot, and bronchoalveolar lavage (BAL) fluids were compared. One subsegment of the right middle lobe and one subsegment of the right lower lobe were lavaged in the same session. Interlobar consistency of neutrophil and eosinophil cell recoveries was observed but, in contrast, the levels of MPO or ECP did not correlate in lavage fluids aspirated from the two lobes. These results suggest that BAL cell content from a single lobe of the lung in healthy subjects does reflect the cell populations throughout the airways, while the levels of soluble proteins may differ between the lobes. Such a variation questions the correlation between cells and their secretory products or the correlation between levels of solutes in lavage fluid and in the underlying tissue. Further methodological studies appear warranted to elucidate whether cell and solute recoveries accurately reflect the underlying pathology.

Lung mechanics and gas exchange during exercise in pulmonary sarcoidosis.

To clarify how lung function at exercise is affected in sarcoidosis, and to analyze how exercise studies compare to testing measurements, 63 patients with pulmonary sarcoidosis were examined with lung mechanics and arterial blood gases during exercise. These findings were compared with simultaneously obtained, but previously reported results of the static lung pressure/volume curve and the lung resistance/static lung pressure curve. While mechanical variables at maximal exercise were as sensitive as those determined by measuring the PstL/V and RL/PstL curves, mechanics during spontaneous breathing at rest was less sensitive. The derangement of mechanics was more evident than that of arterial blood gases. No measurement at rest was a good predictor of working capacity or of arterial PaO2. A comprehensive exercise examination may be an alternative to resting investigations, which are either more elaborate or less sensitive.

Transfer of 99mTc DTPA and bronchoalveolar lavage findings in patients with asymptomatic extrinsic allergic alveolitis.

An investigation was performed to determine whether symptom free patients with previously diagnosed extrinsic allergic alveolitis had signs of inflammation in the lung. Pulmonary clearance of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (DTPA) was measured in seven patients with a history of extrinsic allergic alveolitis but with no symptoms at the time of the study and in 12 control subjects. Monoexponential clearance curves were obtained in all 12 control subjects. In contrast, lung clearance was abnormal in five of the seven patients: biexponential clearance curves were noted in four and an abnormally rapid monoexponential curve in one. Bronchoalveolar lavage was performed in all patients. Fluid from the second and third aliquots showed increased concentrations of albumin and urea in fluids from the patients, suggesting increased plasma leakage through the alveolocapillary membranes. More eosinophils and more eosinophil cationic protein were also found in the lavage fluid from the patients. The trend towards increased numbers of eosinophils in patients with abnormal lung clearance of DTPA suggests that this may be due to a continuing inflammatory reaction. Lung inflammation was also suggested by the fact that less leukotriene B4 was secreted by cultured alveolar macrophages obtained from patients than by control macrophages. It is concluded that symptom free patients with previous extrinsic allergic alveolitis have continuing alveolar disease as shown by lung clearance and lavage findings.

Dosing regimens in the treatment of tuberculosis.

Specific antituberculosis chemotherapy started in the early 1940s. The development of isoniazid in 1952 enhanced the probability of achieving curative therapy. Introduction of rifampicin in the late 1960s and addition of the sterilizing agent pyrazinamide made it possible to shorten the length of treatment and to give it intermittently so that it could be fully supervised. The important principles to consider in the formulation of adequate therapy for tuberculosis are the different bacterial populations and drug resistance. The antituberculosis drugs vary in their bactericidal action, sterilizing action, ability to prevent the emergence of acquired resistance and suitability for intermittent use. The recommended regimen for newly diagnosed patients is a six month daily regimen of isoniazid and rifampicin, supplemented with pyrazinamide for the first two months. Variants of the standard six month regimen are used when fully supervised intermittent chemotherapy can be organised, when there is a high level of initial resistance or if it is suspected that the patient's strain is resistant to isoniazid. The recommended dosages are appropriate for all forms of tuberculosis and are the same for children and adults.

Lung function in progressive systemic sclerosis is dominated by poorly compliant lungs and stiff airways.

Pulmonary function was investigated in 24 patients with progressive systemic sclerosis. The lung volumes were measured by a body plethysmograph. Bronchial and parenchymal properties were studied by relating pulmonary resistance and lung volume to pulmonary elastic recoil pressure. Pulmonary mechanics and arterial blood gases were studied during graded exercise on a bicycle ergometer. The most fundamental abnormality was a less compliant lung parenchyma together with lowered TLC, VC and ventilatory capacity. A mild intrinsic bronchial obstruction was found, irrespective of smoking habits. In 7 patients, resistance did not, however, increase towards residual volume as it does in normal subjects. This phenomenon is interpreted as stiff airways withstanding compression. Blood gas values at rest, and during work, were remarkably normal. There was no correlation between fibrosis judged from static lung compliance and from chest roentgenograms.

Early changes in oesophageal function in progressive systemic sclerosis: a comparison of manometry and radiology.

The characteristics of oesophageal dysfunction were studied with manometry and cine radiography in a recumbent position in 21 patients with typical progressive systemic sclerosis (PSS). Manometry was also performed in a matched control group. Only one patient had a completely normal manometry. Mean resting pressure in both the upper and lower oesophageal sphincters were significantly decreased in PSS. Twelve patients had no detectable peristalsis in the lower oesophagus. In the upper oesophagus, the mean pressure amplitude of the peristalitic wave was found to be lower than normal in all patients with detectable peristalsis. In some patients, the only feature of oesophageal dysfunction observed was an increased speed of the peristaltic wave in the middle and lower oesophagus. This is interpreted as an impaired coordination of the propulsive peristalsis. Neuromuscular dysfunction of the oesophagus in its full length was thus clearly demonstrated. At cine radiography, three patients were judged as normal, and 13 patients had severe impairment of the peristaltic function in the distal two-thirds of oesophagus. Oesophageal scoring based on manometry correlated well to scoring based on radiography. Cine radiography of the recumbent patient gives adequate information for clinical purposes. Detection of early changes in the amplitude and speed of the propagation wave requires manometry.

Factors limiting exercise performance in progressive systemic sclerosis.

In order to evaluate to which extent various organs limit physical performance in PSS, maximal working capacity was studied in 22 patients. Special attention was given to cardiac and pulmonary function, joint mobility, and muscular strength. A model for scoring these parameters is given. Working capacity was on the average 51% of the predicted normal value. Ventilation at maximal workload was high despite normal arterial blood gases and presumably normal physiologic dead space. This can be explained by an increased demand on ventilation from an increased muscle metabolism. This may be due to impeded mobility of respiratory and locomotive organs. The maximal heart rate was low and patients with low physical capacity had only a small decrease in base excess. One third of the patients developed arrhythmia during exercise, which contributed to a low performance. Other myocardial involvement was common, seen in the Q-waves, low voltage, left axis deviation, and increased heart volume. In PSS, these ECG changes probably reflect myocardial fibrosis that has developed without clinically manifest infarction. Special attention must be given to arrhythmias at work, which are overlooked in a resting ECG. Ventricular tachycardia plays an important role in sudden death, which, when it occurs, almost always does so within the first years after the onset of PSS. There was no close linkage between cardiac dysfunction and pulmonary fibrosis or joint-muscle impairment. The scoring system showed an equal distribution in reduction of working capacity as to circulation, pulmonary function, and locomotive function.+2

Cyclofenil versus placebo in progressive systemic sclerosis. A one-year double-blind crossover study of 27 patients.

Cyclofenil was evaluated versus placebo in the treatment of progressive systemic sclerosis (PSS, scleroderma) in a 2 x 6-month double-blind crossover study. The mean duration of disease was six years. Of 38 patients entering the study, 27 completed both periods. Reasons for drop-outs were very high liver transaminases in three cases, cardiac death in two, and drug allergy, alcoholic problems, suspected congestive heart failure, reactivation of tuberculosis, arteriosclerotic heart disease, and lethal progression of PSS in one case each. No fatality was attributed to cyclofenil. Liver enzyme abnormalities were seen in 13 of 35 active drug periods and in 5 of 30 placebo periods. Cutaneous and visceral involvement were assessed by a large battery of subjective parameters and objective tests. Overall improvement was seen during 17 drug periods and nine placebo periods (N.S.), but a paired comparison of the status at the end of each treatment period resulted in the following distribution: 15 were improved at the end of the drug period, four at the end of placebo period (p less than 0.01) and eight were unchanged. In patients with a disease duration of five years or less, joint stiffness and pain were less on drug than on placebo treatment (p less than 0.05). In the whole group, oesophageal peristalsis improved (p less than 0.05). Blood folate increased (p less than 0.01). Working capacity was lower after the drug period than after the placebo period (p less than 0.05). Several other parameters, however, did not change significantly. Cyclofenil appears to be a promising drug in the treatment of PSS and should be tested further in controlled long-term studies.

Improvement of lung function in a scleroderma patient treated for 12 months with cyclofenil.

A 48 year old male scleroderma patient with typical impairment of respiratory function, including low vital capacity, low static lung compliance and low diffusing capacity for carbon monoxide, was treated with cyclofenil for one year. Assessment of lung function after 3, 6 and 12 months treatment showed marked improvement of vital capacity, increased physical working capacity, less hypoxia at maximum work, increase of static lung compliance and decreases of maximal transpulmonary pressure. Closing capacity decreased, and an increase in difussing capacity for carbon monoxide was seen.