Azithromycin reduces pulmonary fibrosis in a bleomycin mouse model.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease without proper treatment. Despite intensive research, the exact underlying pathogenesis remains elusive. It is regarded as a continuous injury, resulting in inflammation, infiltration, and proliferation of fibroblasts and extracellular matrix deposition, leading to an irreversible restrictive lung function deterioration and death. In this study the effect of azithromycin, a macrolide antibiotic on bleomycin-induced pulmonary fibrosis was investigated. C57BL/6 mice were intratracheally instilled with bleomycin (0.5 mg/kg) or saline. In the bleomycin group, half of the animals received azithromycin every other day from day 1 on. Bronchoalveolar lavage and histology were performed at days 7 and 35, and pulmonary function tests on day 35. At day 35, fibrotic lesions (spindle cell proliferation/collagen I deposition) were paralleled by a restrictive lung function pattern. Alterations were found in neutrophils and macrophages (innate immunity) and in T(H)2, T(H)17, and Treg cytokines (adaptive immunity). Azithromycin significantly reduced both fibrosis and the restrictive lung function pattern. This study demonstrated a beneficial effect of azithromycin on bleomycin-induced pulmonary fibrosis. A possible mechanism could be a modulation of both innate immunity and adaptive immunity. These findings might suggest a potential role for azithromycin in the treatment of IPF.

Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis.

The purpose of the present study was to evaluate the accuracy of the diagnosis of idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European countries, and to calculate the interobserver agreement between high-resolution computed tomography reviewers and histology reviewers in IPF diagnosis. The diagnosis of usual interstitial pneumonia (UIP) was assessed by a local investigator, following the American Thoracic Society/European Respiratory Society consensus statement, and confirmed when a minimum of two out of three expert reviewers from each expert panel agreed with the diagnosis. The level of agreement between readers within each expert panel was calculated by weighted kappa. The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases. A total of 179 thoracic high-resolution computed tomography scans were independently reviewed, and an interobserver agreement of 0.40 was found. Open or thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be reviewed by the expert committee. The weighted kappa between histology readers was 0.30. It is concluded that, although the level of agreement between the readers within each panel was only fair to moderate, the overall accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good (87.2%).

Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan in non-small-cell lung cancer: An analysis of 125 cases. Leuven Lung Cancer Group.

PURPOSE: The amount of radio-labeled (18)F-fluoro-2-deoxy-glucose (FDG) uptake, a measurement of the increased glucose metabolism of non-small-cell lung cancer (NSCLC) cells, has recently been correlated with proliferation capacity. The Standardized Uptake Value (SUV), a semi-quantitative measurement of FDG uptake on positron emission tomography (PET) scan, could thus be of prognostic significance. PATIENTS AND METHODS: We analyzed the follow-up of 125 potentially operable NSCLC patients, previously included in three of our prospective PET protocols. Performance status, maximal tumor diameter, tumor-cell type, SUV, and final staging were analyzed for their possible association with survival. RESULTS: Sixty-five patients had stage I or II NSCLC, 37 had stage IIIA, and 23 had stage IIIB. Treatment was complete resection in 91 cases. In a univariate analysis, performance status (P =.002), stage (P =.001), tumor diameter (P =.06), tumor-cell type (P =.03), and SUV greater than 7 (P =.001) were correlated with survival. For SUV, group dichotomy with a cut-off SUV of 7 had the best discriminative value for prognosis, both in the total and surgical cohort. A multivariate Cox analysis identified performance status (P =.02), stage (P =.01), and SUV (P =.007) as important for the prognosis. In the surgical group, patients with a resected tumor less than 3 cm had an expected 2-year survival of 86%, if the SUV was below 7, and 60%, if above 7. Nearly all resected tumors larger than 3 cm had SUV's greater than 7 and an expected 2-year survival of 43%. CONCLUSION: We conclude that the FDG uptake in primary NSCLC on PET has an important prognostic value and could be complementary to other well-known factors in the decision on adjuvant treatment protocols.

Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients.

PURPOSE: To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS: ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION: PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.

Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study.

PURPOSE: To investigate the effects of medroxyprogesterone acetate (MPA) on appetite, weight, and quality of life (QL) in patients with advanced-stage, incurable, non-hormone-sensitive cancer. PATIENTS AND METHODS: Two hundred six eligible patients were randomized between double-blind MPA 500 mg twice daily or placebo. Appetite (0 to 10 numerical rating scale), weight, and QL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ-C30]) were assessed before the start of treatment (t = 0), and 6 weeks (t = 6) and 12 weeks (t = 12) thereafter. RESULTS: One hundred thirty-four patients (68 MPA and 66 placebo) were assessable at t = 6 and 99 patients (53 MPA and 46 placebo) at t = 12. A beneficial effect of MPA on appetite was observed after both 6 weeks (P = .008) and 12 weeks (P = .01) of treatment. After 12 weeks, a mean weight gain of 0.6 +/- 4.4 kg was seen in the MPA, versus an ongoing mean weight loss of 1.4 +/- 4.6 kg in the placebo group. This difference of 2.0 kg was statistically significant (P = .04). During the study, several areas of QL deteriorated in the total group of patients. With the exception of an improvement in appetite and possible also a reduction in nausea and vomiting, no measurable beneficial effects of MPA on QL could be demonstrated. The side effects profile of MPA was favorable: only a trend toward an increase in (usually mild) peripheral edema was observed. CONCLUSION: In weight-losing, advanced-stage non-hormone-sensitive cancer patients, MPA exhibits a mild side effects profile, has a beneficial effect on appetite, and may prevent further weight loss. However, general QL in the present study was not measurably influenced by MPA treatment.

Clinical spectrum of endobronchial tuberculosis in elderly patients.

We describe 11 elderly patients with bacteriologically proved endobronchial tuberculosis, representing 15% of our 73 geriatric patients with pulmonary tuberculosis in the period 1980 to 1987. In seven (64%) of the 11 patients, an incorrect diagnosis was initially made. Cough, mostly nonproductive, was invariably present, and general symptoms (fever, anorexia, weight loss) predominated over specific pulmonary symptoms. The radiographic features were rather "unusual": in only two (18%) of the 11 cases, apicoposterior consolidations with or without cavitation were found. Fiberoptic bronchoscopy showed a range of endobronchial abnormalities that included ulcerations, mass lesions, and fibrostenoses. Antituberculous treatment generally led to satisfactory results. Still, residual bronchostenosis was observed in four (57%) of seven patients in whom a control bronchoscopy was done. In one of these four patients, a pneumonectomy had to be performed for uncontrollable retro-obstructive infections, and in another, repeated endoscopic dilatations were effective. In elderly patients, endobronchial tuberculosis should be considered in the differential diagnosis, especially in the presence of chronic cough. In these patients, the chest roentgenogram may be clear or suggestive of bronchial carcinoma or pneumonitis.

Putrescine uptake in rat type II pneumocytes correlates with gamma-glutamyltransferase activity.

gamma-Glutamyltransferase (gamma GT) is a key enzyme in glutathione metabolism and it is thought also to play a role in the uptake of polyamines such as putrescine. The aim of our study was to investigate if changes in gamma GT activity would alter total putrescine uptake [P(up)(tot)], as well as more specific uptake via the gamma GT pathway [P(up)(gamma GT)]. Forty-eight hours after their isolation, rat type II cells were exposed to 30, 60 or 125 microM L-buthionine-[SR]-sulfoximine (BSO) for 3 hr; 200 or 800 microM tertiary-butylhydroperoxide (t-BOOH) for 40 min; 10, 100 or 1000 microM paraquat (PQ) for 1 hr; and 60 or 85% O2 for 48 hr. The gamma GT activity, P(up)(tot) and P(up)(gamma GT) (assessed by inhibiting gamma GT) were measured immediately after the exposure to hyperoxia, or 24 hr after treatment with BSO, t-BOOH or PQ. From previous studies, it is known that these experimental conditions increased (BSO, 200 microM t-BOOH) or decreased (800 microM t-BOOH, PQ, hyperoxia) gamma GT activity. There was a strong correlation between the changes in gamma GT activity and the changes in P(up)(gamma GT) (r = 0.81, p < 0.001). These findings support the hypothesis that gamma GT partly regulates the uptake of putrescine, one of the polyamines required for cell growth and differentiation.

Increase in gamma-glutamyltransferase by glutathione depletion in rat type II pneumocytes.

The purpose of our study was to investigate the effect of oxidative stress or intracellular glutathione (GSH) depletion on gamma-glutamyltransferase (gamma-GT) activity in cultured type II pneumocytes. Twenty-four hours after isolation, primary cultures of rat type II pneumocytes were preincubated with one of four compounds: 15, 30, 60, 125, 250 microM L-buthionine-[SR]-sulfoximine (BSO) for 3 h; 100, 200, 400, 800 microM tertiary-butylhydroperoxide (t-BOOH) for 45 min; 10, 25, 50, 100 microM menadione for 15 min; 100, 1000 microM paraquat for 1 h. GSH levels, H2O2 and O2.- generation were measured immediately after the incubation, gamma-GT activity and GSH levels also up to 24 h or 48 h later. Exposure to BSO led to a persistent GSH depletion without increase in H2O2 or O2.- production, together with a dose and time-dependent increase (doubling) of gamma-GT activity with a nonsignificant increase in gamma-GT mRNA expression 24 h after exposure to BSO. Exposure to 100 microM menadione, which increased H2O2 production, decreased gamma-GT activity. t-BOOH or paraquat did not give rise to a measurable increase in H2O2 or O2.-. Paraquat did not affect initial GSH levels, but increased GSH and decreased gamma-GT activity 24 h later. t-BOOH (400 and 800 microM) initially decreased GSH, and tended to increase GSH 24 h later, 100 and 200 microM increased gamma-GT activity 24 h later, but 800 microM decreased it. Restoration of intracellular GSH levels by addition of GSH to the culture medium completely prevented the increase in gamma-GT activity by BSO, while the addition of catalase or DMTU had no effect. We conclude that at least two effects are operating upon gamma-GT activity: GSH depletion seems to increase gamma-GT activity, while exposure to compounds generating oxidative stress correlates with a decrease in gamma-GT activity.

The role of thiol oxidation in Cobalt(II)-induced toxicity in hamster lung.

Exposure of lung tissue to Co(II) ions both in vivo and in vitro results in toxicity, a relatively early event of which is the oxidation of cellular glutathione. In this study we have attempted to delineate the relationship between this oxidation of glutathione and the subsequent development of cellular dysfunction. Simultaneous incubation with H2O2 potentiated Co(II)-induced increases in both levels of oxidized glutathione (GSSG) and the activity of the pentose phosphate pathway in hamster lung slices. This effect was initially synergistic and, thereafter, both parameters were maintained at significantly greater levels than with either treatment alone throughout the incubation period until the onset of detectable cellular dysfunction. When dysfunction occurred, however, it was not quantitatively increased by the co-treatment over that occurring with CoCl2 alone. Similarly, pretreatment of slices with the glutathione reductase inhibitor 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) potentiated the Co(II)-induced increase in levels of GSSG. However, this effect was again not associated with an enhancement of cell dysfunction. Since the Co(II)-induced cell damage appeared not to be related directly to the oxidation of glutathione, the quantitative significance of the latter was investigated by comparison with the known oxidant tert-butyl hydroperoxide (t-BOOH). At a concentration of 100 microM, t-BOOH caused an increase in the concentration of GSSG in BCNU-pretreated lung slices which was comparable to that after treatment with Co(II)/H2O2 or CO(II)/BCNU. None of these treatments resulted in a loss of protein thiols. Furthermore, in contrast to Co(II), t-BOOH/BCNU treatment did not result in impaired cell functions. However, at a t-BOOH concentration of 250 microM, t-BOOH/BCNU treatment caused a significantly greater increase in the level of GSSG than that caused by the previous treatments and was associated with both a loss of protein thiols and increased cell dysfunction. We have concluded from these data that under our experimental conditions, Co(II)-induced cell dysfunction is not a consequence of oxidation of cellular glutathione. The reason for this appears to be that the extent of glutathione oxidation by Co(II) even at a concentration which induces cell dysfunction is not of sufficient magnitude to result in the oxidation of protein thiol groups, an event which is likely to constitute the critical consequence of glutathione oxidation in the toxic process.

Putrescine and paraquat uptake in human lung slices and isolated type II pneumocytes.

Paraquat is accumulated into the lungs of various species by an active uptake system which also appears to mediate the uptake of endogenous polyamines, such as putrescine. The accumulation of putrescine in the human lung has been previously shown to be mainly located in the type II cells. In the present study, we have studied the mutually competitive inhibition of putrescine and paraquat in human lung slices and the inhibition of putrescine by paraquat or cystamine in isolated human type II pneumocytes. Peripheral lung tissue taken from patients undergoing pneumectomy or lobectomy was used. The initial steps of the cell isolation procedure differed from the literature in that the tissue was first sliced in 0.7 mm thick slices, which were washed in phosphate buffered saline without calcium and magnesium (PBS-), followed by incubations with trypsin. The type II cells were purified and isolated by differential adherence on plastic followed by Percoll gradient centrifugation. Uptake was determined 48 hr after cell isolation. The accumulation of radiolabelled putrescine showed saturation kinetics, with the following apparent kinetic parameters: Km 6.7 and 6.2-7.6 microM and Vmax 2.7 and 3.0-3.4 mumol/g prot/hr for slices and isolated cells, respectively. In the presence of paraquat, putrescine uptake was reduced, in both systems, in a manner compatible with competitive inhibition, with calculated inhibition constants (Ki) of 549-614 and 659-895 microM paraquat for slices and isolated cells, respectively. The accumulation of putrescine in isolated human pneumocytes was strongly reduced in the presence of cystamine, with calculated Ki of 3.7 microM cystamine. These data indicate that putrescine, paraquat and cystamine accumulate in the human lung by the same uptake system, but that the affinities for the three substrates differ. The presence of an uptake system for putrescine in cultured human pulmonary type II is probably useful as a functional viability test.

Role of gamma-glutamyltransferase in putrescine uptake by rat type II pneumocytes.

Putrescine uptake in type II pneumocytes is a carrier-mediated active process. Our hypothesis was that oligoamines might be taken up into the cell at least in part by gamma-glutamyltransferase (gamma-GT). This was investigated in rat type II pneumocytes 24 hr after their isolation. Preexposure to 125 microM L-buthionine-[SR]-sulfoximine (BSO) or 100 microM diethylmaleate (DEM), both of which affect intracellular glutathione (GSH) only, were found to decrease GSH by 85% (p < 0.05) and 62%, respectively (p < 0.05), without change in [3H]-putrescine uptake. Preexposure to 20 microM N-ethylmaleimide (NEM), which affects intra- and extracellular GSH, decreased intracellular GSH by 79% (p = 0.015) and putrescine uptake by 39% (p = 0.03). Selective extracellular GSH depletion by 10 microM copper-o-phenanthroline complex (CuP) led to a decrease in putrescine uptake of 41% (p = 0.001), while intracellular GSH remained unchanged. Specific inhibition of gamma-GT by 5-20 mM serine-borate or 5 mM acivicin gave similar degrees of putrescine uptake inhibition (39.5% and 40.5%). The kinetic properties of the putrescine uptake system in the presence of acivicin and serine-borate indicated that the Vmax decreased by 25%, while Km remained unchanged. In experiments with pure gamma-GT, the oligoamines putrescine, spermidine and spermine, and cystamine proved to be acceptor substrates for gamma-GT, all having similar efficiencies (Vmax/Km); methylglyoxal-bis-(guanyl-hydrazone) and paraquat were not accepted. As extracellular GSH is required for gamma-GT, and because its extracellular depletion inhibits putrescine uptake as much as specific inhibition of gamma-GT, we suggest that 30-40% of the putrescine uptake in type II pneumocytes occurs by gamma-GT and that, therefore, at least two systems are involved in the uptake of putrescine.

Early emphysema. Ten years' evolution.

In this study, functional evolution over ten years was evaluated in 13 patients with early emphysema. The diagnosis was made on the basis of a decrease in single-breath DCO (55 +/- 14 percent predicted, mean +/- 1 SD), a loss of elastic recoil (CL,st = 0.76 +/- 0.25 L/cm H2O), and only minor airway obstruction (FEV1 = 87 +/- 13 percent predicted, Sgaw = 0.09 +/- 0.04 cm H2O-1.s-1), and compatible chest radiographs. During the ten years, there was a decrease in FEV1 of 0.89 +/- 0.40 L p less than 0.001), with a range of 0.20 to 1.55 L (which could not clearly be related to smoking habits or to initial lung function), a decrease in elastic recoil (p less than 0.05, with a decrease of Ptp, TLC by 6 +/- 7 cm H2O; p approximately equal to 0.05), an increase in TLC of 0.46 +/- 0.80 1 (p approximately equal to 0.05), and in RV/TLC of 9 +/- 3 percent (p less than 0.001). The resistance of the upstream segment (ratio Ptp/Vmax) increased slightly but generally remained within normal limits. In conclusion, patients with early emphysema resemble those with classic COPD, with a mean yearly decline in FEV1 similar to that in COPD.

Four-stage tuberculin testing in elderly subjects induces age-dependent progressive boosting.

We administered four sequential tuberculin skin tests (5 TU, PPD) with intervals of one week to 223 subjects older than 65 years of age to evaluate whether elderly subjects demonstrated progressive boosting. Indurations of at least 10 mm with increases of at least 6 mm (over the previous test) were considered significant reactions, and these were found in 29 percent of the subjects after test 1, in 43 percent after test 2, in 53 percent after test 3, and in 57 percent after test 4 (p less than 0.05), ie, only about 50 percent of all the positives were detected after the first test. The percentage of positive reactors was inversely related to age (p less than 0.001), yet this age-dependent difference decreased with increasing number of tests. For the 65- to 74-year-old age group, 44 percent reacted positively after the first test and after three tests almost a plateau of 65 to 70 percent positive reactors was reached, suggesting that a minority only of about 30 to 35 percent of these geriatric patients might have outlived their bacilli or were never infected. For the 75- to 84-year-old age group, 24 percent reacted after the first test and 55 percent reacted after the fourth one. For the older than 85-year-old age group, 19 percent positive reactors were found after the first test and 46 percent were found after the fourth test, without clear-cut leveling off toward a plateau value, suggesting that additional tests would induce further boosting. Mean diameters of positive reactions were 15 to 24 mm, and were mostly at least 12 mm larger than in the previous tests. These data support the hypothesis that the negative tuberculin reaction, which is often found in elderly subjects, is mainly due to the failing immune response to tuberculin antigen that can be restored progressively by repeated administrations. These findings, furthermore, emphasize that especially in elderly, care should be taken not to interpret a boosting reaction as a conversion and especially that neither a two-step testing as recommended by the ATS and CDC (Am Rev Respir Dis 1990; 142:723-35) nor even a four-step testing may suffice to detect all positives in this type of population.

Preoperative and postoperative abnormalities in chest x-ray indices and in lung function in pectus deformities.

In 88 patients with pectus deformities radiologic chest indices and routine pulmonary function tests were measured before and 1 to 20 years after corrective surgery. A combination of anteroposterior indices at the upper and lower level of the chest were investigated to quantitate and to discriminate the different pectus deformities. The study comprised four groups: pectus excavatum, pectus carinatum, pectus deformatum and pectus excavatum with scoliosis. These indices were also assessed in 250 healthy males and females. Generally, several indices showed significant and discriminative changes in the different patient groups and improved again after surgery. Preoperative lung function was decreased in pectus excavatum only. In all groups lung function worsened after surgery. A stepwise discriminant analysis performed on the large group with pectus excavatum indicated that postoperative lung function was decreased if the preoperative value of FEV1 or VC was more than about 75 percent predicted and vice versa, but that it was not related to other factors such as radiologic indices, age at operation or time since operation.

Eosinophilic pneumonia without radiographic pulmonary infiltrates.

In a 52-year-old man, chronic eosinophilic pneumonia (CEP), suggested by clinical history and marked eosinophilia in the peripheral blood and in the bronchoalveolar lavage fluid, has been diagnosed on open lung biopsy. Nevertheless, chest roentgenograms never showed any infiltration during the course of the disease. Extensive etiologic examination remained negative. Steroid therapy induced a dramatic clinical response, disappearance of the eosinophilia in the peripheral blood and in the bronchoalveolar lavage fluid, and quick normalization of pulmonary function. We suggest that a typical history and markedly eosinophilic alveolitis allows one to make the diagnosis of CEP even in the presence of normal chest film findings.

No paradoxical bronchodilator response with forced oscillation technique in children with cystic fibrosis.

STUDY OBJECTIVES: The aim of the present study was to evaluate the forced oscillation technique (FOT) in cystic fibrosis (CF) children and to participate in the discussion about the usefulness of beta2-antagonists in CF. DESIGN: Pulmonary function was measured with spirometry, body plethysmography, and FOT before and after inhalation of 200 microg of albuterol (salbutamol). The following were collected: vital capacity (VC), FEV1, FEV1/VC, airway resistance (Raw), thoracic gas volume, respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at 6 Hz (Rrs6 and Xrs6), and resonance frequency. SETTING: The study was set up at a university hospital with a CF population of 125 children and adolescents. PATIENTS: Data were collected on 20 patients in stable condition able to perform the three lung function tests. MEASUREMENTS AND RESULTS: Mean baseline values (+/-SD) were 0.36+/-0.15 kPa/L/s for Raw, 0.5+/-0.15 kPa/L/s for Rrs6, and 61+/-22% predicted for FEV1. The relationship between FEV1 and Raw or Rrs6 was poor. Xrs6 and FEV1/VC correlated weakly (r=0.56; p < 0.05). After bronchodilator administration, the mean changes +/-SD in percent of baseline were +3 +/- 11% for FEV1, -16 +/- 22% for Raw, and -16 +/- 9% for Rrs6. In six patients, a paradoxical decrease in FEV1 was measured but an increase in Rrs6 was never found; in two patients, an increase of Raw of < 10% was found. In 13 patients, the decrease of Rrs6 was > 12%. CONCLUSIONS: The results suggest that FOT measurements cannot replace baseline spirometric measurements in CF, but that the evaluation of the effect of beta2-agonists on the airway diameter in CF should include an FOT measurement.

Cobalt-induced bronchial asthma in diamond polishers.

Three diamond workers had occupational asthma attributed to the inhalation of cobalt powder. The exposure originated from high speed polishing disks with an abrasive consisting of microdiamonds cemented in extra fine cobalt not alloyed to tungsten carbide. The bronchoconstriction progressed towards the end of working-days; it was especially pronounced in the absence of an adequate exhaust ventilation; and it could be accompanied by rhinitis and chest tightness. Cobalt inhalation challenge tests were positive in all three patients, and exposure to cobalt temporarily increased nonspecific hyperreactivity.

Measurement of lung density by means of quantitative CT scanning. A study of correlations with pulmonary function tests.

In recent years, much attention has been given to the role of CT in detecting and quantitating pulmonary emphysema. We measured CT lung density in 45 patients undergoing a diagnostic work-up and compared this with pulmonary function tests. The CT lung densities measured with the sector method and with the whole lung method were very highly correlated with each other (r = 0.96, p less than 0.001), and measurements at TLC systematically gave a lower density than those at FRC (p less than 0.001). Also, CT density measurements at TLC and even more so at FRC correlated well with pulmonary function indices of airway obstruction and of hyperinflation, but not with indices that are considered more specific for emphysema (single breath DCO, static lung compliance) We conclude that CT lung-density gives a good reflection of the degree of hyperinflation, ie, enlargement of distal airways, but is not sensitive to detect whether or not this is associated with emphysema.

Diagnostic value of blood pool and transmission scan in cardiovascular and tissue pathology of the thoracic midline.

We reviewed 48 records of combined blood pool and transmission scans, performed in the last three years for mediastinal masses and cardiomegaly. The purpose was to investigate the diagnostic value of this radioisotopic examination, and in particular to compare it with the roentgenographic examination. The accuracy of both methods in visualizing mediastinal tumors or tissue pathology was very similar. The scintigraphic examination was superior for the diagnosis of cardiovascular pathology. False negative results occurred more frequently than false positives, especially in cases of tumors and aneurysms.