The time course of pulmonary transfer factor changes following heart transplantation

OBJECTIVE: The pulmonary transfer factor for carbon monoxide (TLCO) has been reported to decline following heart transplantation, but the time course of this decline is not well documented. The aim of this study was to define the longitudinal changes in TLCO after heart transplantation. METHODS: Single breath TLCO, lung volumes and expiratory flow rates were prospectively measured in 57 patients (mean age 49 years, range 19-61) before and at least once after heart transplantation. Thirty seven of the 57 patients had four post-transplant assessment which were performed at 6 weeks, 3, 6 and 12 months in 26 patients and at 12, 18, 24 and 36 months in 11 patients. Results were compared with data from 28 normal subjects (mean age 40 years, range 19-61). RESULTS: Before transplantation there was a mild impairment of lung volumes and expiratory flow rates. At 6 weeks after transplantation, there was a further reduction in the forced expiratory volume in one second, forced vital capacity, residual volume and total lung capacity, but all of these increased in the subsequent measurements to exceed their pre-transplant values at about 1 year after transplantation. Haemoglobin-corrected TLCO was also reduced before transplantation compared to normal controls (74.3% and 98.6% of predicted respectively, P < 0.001). Although TLCO per unit alveolar volume (KCO) was relatively preserved in heart transplant candidates, it was still significantly lower than that of normal controls (92.6% and 105.3% of predicted respectively, P < 0.05). After transplantation, mean haemoglobin-corrected TLCO and KCO declined by 12% and 20% of predicted respectively) with the majority of patients having reductions greater than 10% of predicted. The decline in TLCO and KCO was evident at 6 weeks after transplantation with no further changes in the subsequent measurements. CONCLUSIONS: TLCO is reduced in heart transplant candidates and declines further after heart transplantation despite improvement in lung volumes and airway function. The early and non-progressive nature of TLCO decline suggests an aetiology exerting its effect on TLCO within the first 6 weeks after transplantation.     

The value of forced expiratory volume in 1 s in screening subjects with stable COPD for PaO2 < 7.3 kPa qualifying for long-term oxygen therapy

Guidelines on the management of chronic obstructive pulmonary disease (COPD) issued by the European Respiratory Society (ERS), British Thoracic Society (BTS), American Thoracic Society (ATS), and Department of Health for England and Wales (DoH) suggest differing values of forced expiratory volume in 1 s (FEV1) below which arterial blood gas analysis should be performed to determine the presence of severe hypoxaemia and possible long-term oxygen therapy (LTOT) requirement. This study aimed to determine the value of FEV1 at these different levels in screening for LTOT requirement defined as PaO2 < 7.3 kPa in subjects with stable COPD. Comparative measures were taken against other lung function tests of volume and diffusing capacity. A retrospective analysis of paired lung function and arterial oxygen measurements in 491 subjects was made. The positive and negative predictive values, sensitivity and specificity of FEV1 < 70% predicted (ERS), FEV1 < 50% predicted (ATS), FEV1 < 40% predicted (BTS) and FEV1 < 1.51 (DoH) were determined for fulfilling LTOT criteria (PaO2 < 7.3 kPa). The correlation between lung function variables and PaO2 was established. Logistic regression analysis was used to classify subjects with PaO2 < 7.3 kPa and PaO2 > or = 7.3 kPa. Using FEV1 to screen for LTOT requirement produced a high negative predictive value at all four suggested limits (FEV1 < 70% 100%, FEV1 < 50% 96%, FEV1 < 40% 95%, FEV1 < 1.51 97%). However, the positive predictive values were low (FEV1 < 70% 13%, FEV1 < 50% 16%, FEV1 < 40% 19%, FEV1 < 1.51 15%) as were sensitivities. No single lung function variable was a strong determinant of PaO2. FEV1 % pred (r = 0.40), FVC % pred (r = 0.34) and TLCO % pred (r = 0.27) had the strongest relationships. Logistic regression also placed FEV1 % pred and TLCO % pred as the best predictors of PaO2 < 7.3 kPa. We conclude no lung function variable correlates well with PaO2 in subjects with stable COPD. The best predictor of PaO2 < 7.3 kPa was FEV1 % pred. Whilst a low FEV1 is a poor predictor of LTOT requirement in an individual, PaO2 < 7.3 kPa is only found in subjects with a low FEV1. A high FEV1 may be used to exclude subjects from further investigation for LTOT and prevent unnecessary arterial sampling.     

Two cases of adult Still''s disease with atypical rash

Previous studies on baseline pulmonary function testing (PFT) abnormalities in patients with inflammatory bowel disease (IBD) are conflicting because most of them have incorporated patients suffering from both ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study is to investigate whether any PFT abnormalities could be detected in a large group of IBD patients and whether there are differences between the two IBD entities. A total of 132 patients, 47 with CD (mean age 35 years) and 85 with UC (mean age 40 years) were studied. Pulmonary function tests (PFTs), lung transfer factor for carbon monoxide (TLCO) were examined and compared with those of 36 healthy controls. No significant difference of mean values of spirometric indices, TLCO and ABG was found between the two groups of patients and controls, or between patients with CD and UC. However, nine (19%) patients with CD and 15 (17.6%) with UC had a reduction in TLCO, a percentage significantly higher than in controls (P < 0.05). The majority of the patients with TLCO reduction were in an active phase of disease (P < 0.05). Our results suggest that there is no difference in routine PFTs between UC and CD patients, as well as between both these groups and normal controls. However, TLCO abnormalities related to the degree of disease activity are found in patients with both UC and CD.     

Pulmonary function in patients with trophoblastic disease treated with low-dose methotrexate

The Sheffield Trophoblastic Disease Centre treats about 25 patients with persistent trophoblastic disease each year. A total of 75% of patients are classified as low risk according to the Charing Cross Hospital prognostic scoring system and receive methotrexate (MTX) 50 mg, i.m., on days 1, 3, 5, 7 with folinic acid 7.5 mg orally 24 h after each methotrexate injection. There is a 7-day rest between treatment cycles. Remission is achieved in 85% of cases. Approximately 20% of patients experienced pleuritic chest pain and dyspnoea. We have evaluated prospectively lung function in 16 low-risk patients receiving methotrexate. All patients had pulmonary function tests [spirometry-forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and transfer factor - TLCO, kCO] performed before and after completed treatment. A mean of 7.5 cycles of MTX were administered (range 4-11). There was a significant reduction in the mean TLCO (mean pre/post 8.15/7.38 mmol min-1 kPa-1, P = 0.01), but there were no other statistically significant changes. Three patients experienced respiratory symptoms and were found to have a 39%, 28%, and 11% reduction in TLCO from baseline, improving on follow up to pretreatment levels. Low-dose MTX is an effective therapy but may cause troublesome pulmonary toxicity.     

Mapping of somato-sensory evoked potentials (SEP): new findings suggesting the role of brain waves as a "temporal analyzer of the stimulus"

Patients with multiple sclerosis (MS) show a poor exercise tolerance. A reduction in respiratory muscle strength has also been reported. The purpose of this study was to evaluate whether reduction in exercise tolerance was related to respiratory muscle dysfunction. Twenty four multiple sclerosis patients (mean +/- SD age: 48 +/- 9 yrs, duration of illness 12.2 +/- 6 yrs, severity of illness as assessed by Expanded Disability Scale Score (EDSS) 5.3 +/- 2), underwent detailed evaluation of lung function tests, arterial blood gas analysis, respiratory muscle strength and endurance, and exercise test on an arm ergometer. Sixteen of the 24 patients were able to perform the exercise test (Group I), whilst the other eight were not (group II). Arterial blood gases and lung function tests were normal for both groups. Respiratory muscle strength as assessed both by maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) was significantly reduced (MIP 18-76 cmH2O; MEP 16-82 cmH2O) compared to predicted values. Inspiratory muscle endurance time was significantly reduced in Group II in comparison to Group I (247 +/- 148 vs 397 +/- 154 s, respectively). Both MIP and MEP were significantly related to inspiratory muscle endurance time. Endurance time, MIP and MEP were inversely significantly related to duration of illness, whilst only endurance time was significantly related to Expanded Disability Scale Score.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epithelial repair in asthma. Do the benefits of house dust mite avoidance result from proteinase avoidance?

OBJECTIVE: To describe the timing of recovery of lung function after severe acute hypoxemic respiratory failure (AHRF) in children. DESIGN: A serial observational follow-up study of clinical and lung function measurements up to 53 months after acute illness. SETTING: University pediatric intensive care unit in a national children's hospital. PATIENTS: Five critically ill children aged 5-14 years. INTERVENTIONS: None RESULTS: Clinical recovery: each patient required a 3-5 month convalescence before being able to attend full-time school because of lethargy and dyspnea. All patients developed wheeze 3-12 months after illness and four received long-term bronchodilator therapy. Lung function recovery: for both the forced vital capacity (FVC) and forced vital capacity in the first second (FEV1) four patients had abnormally low values, regaining only 60-70% of predicted values for their height and sex, and all of this improvement had occurred by 6-12 months after illness. Beyond this interval, patients remained on their same FVC and FEV1 centile. FEV1/FVC ratios were consistently within the normal range, indicating a predominantly restrictive defect. Changes in peak expiratory flow exhibited a time course of improvement similar to the other lung function tests. CONCLUSION: In children, pulmonary recovery after severe AHRF may occur for 6-12 months. A 1-year follow-up could offer a rational single point for assessment of outcome and long-term counselling of child and parents.     

Partial pulmonary sympathetic denervation by thoracoscopic D2-D3 sympathicolysis for essential hyperhidrosis: effect on the pulmonary diffusion capacity

In patients with essential hyperhidrosis (EH), a pathological condition characterized by increased activity of the upper dorsal sympathetic ganglia D2-D3, anatomical interruption at the D2-D3 level by thoracoscopic sympathicolysis (TS) is a safe and effective treatment. The D2 and D3 ganglia, however, are also in the pathway of sympathetic lung innervation, which may influence the pulmonary diffusion capacity for carbon monoxide (expressed as transfer factor for CO:TLCO, and as transfer coefficient for CO:KCO). We therefore studied the effect of TS on TLCO and KCO in 50 EH patients: compared with pre-operative values, both TLCO (-6.7%, P < 0.001) and KCO (-4.2%, P = 0.002) were significantly decreased at 6 weeks after bilateral TS, an effect which was independent of the smoking status of the patients. In order to explain this phenomenon, the following pharmacological interventions were studied: (1) oral beta 1 + 2-adrenoreceptor blockade with propranolol caused a comparable decrease of TLCO (-6.3%) and KCO (-7.5%) in matched normal subjects, but had no effect on TLCO and KCO in EH patients prior to TS; and (2) subsequent inhalation of the beta 2-adrenoreceptor agonist salbutamol in a dosage suspected to cause alveolar beta-receptor stimulation had no effect on TLCO and KCO, neither in the normal subjects, nor in EH patients (before and after TS). Although the exact mechanism of the TS-induced decrease in TLCO and KCO remains speculative, these findings suggest that they may be related to a beta 1-adrenoreceptor-mediated change in pulmonary capillary membrane permeability, although TS-induced changes in pulmonary blood flow or an interplay of both mechanisms cannot be excluded.     

Renal excretion of sodium in individuals with stabilized renal graft function

In subjects with a transplanted kidney frequently tubular functions are impaired even when the glomerular filtration is within the normal range. In the present work the authors are dealing in more detail with the problem of tubular sodium reabsorption in the transplanted kidney. The purpose of the investigation was to assess to what extent these changes can be explained as the consequence of adaptational changes due to reduction of the number of nephrons and whether these changes have to be taken into consideration in the differential diagnosis of acute changes of graft function. The glomerular filtration rate (GF) was assessed on the basis of polyfructosan clearance, fractional sodium and potassium excretion (FENa and FEK) in a group of 12 subjects with a stabilized function of a transplanted kidney (group A), in 11 subjects after nephrectomy in healthy donors for transplantation (group B) and in 27 subjects after nephrectomy indicated for a pathological process in one kidney (group C). The mean values of GFR were as follows: Group A: 1.21 (+/- 0.19)ml/s/1.73 sq.m Group B: 1.19 (+/- 0.17)ml/s/1.73 sq.m Group C: 1.24 (+/- 0.21)ml/s/1.73 sq.m The mean values of GFR in different groups did not differ significantly. The mean values of FENa in different groups were as follows: Group A: 3.02 (+/- 1.59)% Group B: 2.05 (+/- 0.77)% Group C: 2.01 (+/- 1.17)% The mean value of FENa in group A was significantly higher than the mean value in group B (p < 0.01) and in group C (p < 0.01). The assembled findings support the idea that reduced tubular sodium reabsorption in the transplanted kidney (with a stabilized value of GFR) cannot be explained only as a manifestation of adaptation of tubular function as a result of the reduced number of functioning nephrons. The persisting osmotic sodium diuresis in the transplanted kidney must be viewed from the aspect of possibly impaired water preservation and the development of dehydration associated with a drop of GFR and must be differentiated from rejection.     

Long-term alterations in growth factor mRNA expression following seizures

Pneumocystis carinii pneumonia (PCP) is one of the most predominant opportunistic infectious diseases in patients with AIDS. Nested PCR has been described as a sensitive and specific tool for detecting P. carinii DNA in clinical specimens. Little is known about the correlation of positive PCR results and clinical evidence of PCP in patients with different forms of immunosuppression. One hundred and thirty-six sputum samples, 26 tracheal-bronchial aspirate samples, 35 bronchoalveolar lavage samples, and 11 lung biopsy samples from (i) human immunodeficiency virus (HIV)-infected patients with AIDS, (ii) immunocompromised patients with leukemia or lymphoma, and (iii) immunocompetent control patients were investigated by a nested PCR amplifying DNA from the mitochondrial large subunit of P. carinii. All patients suffered from acute episodes of respiratory disease. The resulting data were correlated with clinical evidence of PCP. A high degree of association of positive P. carinii PCR results and clinical evidence of PCP in HIV-infected patients with AIDS was found. When calculated for bronchoalveolar lavage and lung biopsy samples, the positive and the negative predictive values of P. carinii PCR for PCP diagnosis in HIV-infected patients with AIDS were 1 and the specificity and the sensitivity were 100%. In contrast, in the group of patients with leukemia or lymphoma, the positive predictive value of the nested PCR for these materials was found to be as low as 0.09, the negative predictive value was 0.73, the specificity was 44.4%, and the sensitivity was 25.0%. No P. carinii DNA could be detected in specimens from immunocompetent patients. In summary, in contrast to patients with leukemia and lymphoma, nested PCR seems to be a sensitive and specific tool for PCP diagnosis in HIV-infected patients with AIDS.     

Long-term effect of Helicobacter pylori eradication on gastric metaplasia in patients with duodenal ulcer

Thyroid functions were analyzed before, during and after interferon (IFN) therapy in patients with chronic hepatitis C. According to the results of routine thyroid function tests and measurements of the levels of anti-thyroid autoantibody prior to the therapy, patients were divided into 2 groups; Group A (19 patients) had at least one abnormal finding related to the thyroid, and Group B (40 patients) did not show any abnormality. Five patients (26%) in Group A and 4 (10%) in Group B showed thyroid dysfunctions which were very clearly reflected by thyrotropin (TSH) measurements. Interestingly, the time of peak TSH elevation in Group A (mean +/- SD, 4.3 +/- 0.8 months) was significantly earlier than that in Group B (6.8 +/- 0.8). Most patients in Group B were diagnosed as having destructive thyroiditis. These findings may suggest that the pathogenesis of IFN-induced thyroid dysfunction consists not only of exacerbation of pre-existing thyroid autoimmunity but also of de novo destructive changes even in the intact thyroid before IFN therapy.     

Physical and biological predictors of changes in whole-lung function following thoracic irradiation

PURPOSE: To develop methods of predicting the pulmonary consequences of thoracic irradiation (RT) by prospectively studying changes in pulmonary function following RT. METHODS AND MATERIALS: 100 patients receiving incidental partial-lung irradiation during treatment of tumors in or adjacent to the thorax had whole-lung function assessed via symptoms and pulmonary function tests (PFTs: FEV1-forced expiratory volume 1 s; DLCO-diffusion capacity) before and repeatedly 6-48 months following RT. All had computed tomography-based three-dimensional (3D) dose calculations with lung density heterogeneity corrections for dose-volume histogram (DVH) and normal tissue complication probability (NTCP) calculations. Functional DVHs (DVfH) based on SPECT (single photon emission computed tomography) lung perfusion scans, and serial transforming growth factor-beta (TGF-beta1) levels were available in 50 and 48 patients, respectively. The incidence and severity of changes in whole-lung function were correlated with clinical, physical, and biological factors. Exploratory statistical analyses were performed using chi-square, Pearson correlations, logistic regression, and multiple linear regression. RESULTS: RT-induced symptoms developed in 21 patients. In the overall group, the single best predictor for the development of symptoms was the NTCP (p < 0.05). Pre-RT PFTs alone were less predictive (p = 0.1 for FEV1, p = 0.08 for DLCO). A multivariate model based on pre-RT DLCO and CT-based NTCP was strongly predictive for the development of symptoms (p < 0.001). NTCPs based on SPECT-derived DVf Hs and TGF-beta1 levels did not appear to provide additional predictive value. The presence or absence of pulmonary symptoms was correlated with the decline in PFT 6 months following RT (p < 0.05). In the overall group, the degree of decline in PFTs was not well correlated with any of the dose-volume variables considered. In patients with "good" pre-RT PFTs, there was a relationship between the percent reduction in PFT and dose-volume parameters such as the percent of lung volume receiving > 30 Gy (p < 0.05). CONCLUSION: The extent of alteration in whole-lung function (symptoms or PFT changes) appears to be related to both dose-volume and pre-RT PFT parameters. The data suggest that no one variable is likely to be an adequate predictor and that multivariate predictive models will be needed. Additional studies are underway to develop better predictive models that consider physical factors such as the DVH and regional perfusion, as well as biological/clinical factors such as pre-RT PFTs and TGF-beta1.     

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part I: Variability of pulmonary function measures

The acute and subacute effects of ambient concentrations of ozone on lung function have been studied extensively in a variety of settings. Such studies generally have focused on measures of function that reflect either lung volumes or flows that are influenced by the physiology of large and small airways (e.g., forced expiratory volume in one second [FEV1). Data from animal studies suggest that the effects of prolonged exposure to elevated ambient concentrations of ozone result in abnormalities in the centriacinar region of the lung; and dosimetry models for humans predict that long-term exposure to ozone could impact the same areas of the human lung. However, alterations in structure at this level of the lung are not well reflected by measuring FEV1 until substantial structural changes have occurred. Measures of the lung function that reflect the functional mechanics of airways smaller than 2 mm in diameter are considered to be more relevant. At least one epidemiologic study has provided evidence that small-airway functions may be relevant to effects of prolonged exposure to environments with high concentrations of oxidants. A considerable body of physiologic data has established that flow rates measured during the terminal portion of a maximum expiratory flow-volume (MEFV) curve are largely governed by airways smaller than 2 mm in diameter A similar interpretation has been given to changes in the slope of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve. Despite the attractiveness of these measures in relation to airway physiology, some data suggest that measurements of flow via the terminal portions of MEFV and SBNW curves have much greater within-subject variability than forced vital capacity (FVC and FEV1. The present study was undertaken as part of a larger feasibility study to develop methods to study the effects of prolonged exposure to elevated ambient ozone levels on lung function in adolescents. A convenience sample of 239 freshmen (ages 16-20 years) entering the University of California, Berkeley were recruited to participate in this protocol. All were lifelong residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were studied on two occasions five to seven days apart. At each test session, subjects performed up to eight forced expiratory maneuvers to produce three acceptable and reproducible MEFV curves by modified American Thoracic Society criteria. Tests of SBNW were then performed on the basis of detailed criteria for validity and reproducibility. Eight attempts to generate three curves were allowed. The delta N2 was obtained by a least-squares regression of nitrogen concentrations between the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and delta N2 were the principal outcomes. Variance components were estimated with a nested random effects model with adjustments for important covariates. The average within-subject coefficients of variation (+/-SD of distribution of means) for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8 (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4 (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/-17.0). The variance attributed to test session was less than 1% for all measures. The percentages of variance due to within-subject variation for each measure (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1 3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested, 234 (97.9%) could provide at least two acceptable MEFV curves, but only 218 (91.2%) could provide at least two acceptable SBNW curves. The results were unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)     

The measurement of the single-breath transfer factor for carbon monoxide and its components using the Morgan Transflow system

In contrast to the standard single-breath transfer factor for carbon monoxide (TLCO), there are no specific guidelines or recommendations for the measurement of its components, the pulmonary capillary blood volume (VC) and membrane component (DM), by the Roughton and Forster method. Ten randomly selected heart transplant patients (three life-long non-smokers, seven ex-smokers > 1 yr, age range 24-55 years) were assessed on two occasions using either the standard or high-oxygen mixture as the first inspired gas in random order. Ten normal subjects (all non-smokers, age range 23-54 years) were assessed on two occasions using either a long protocol (30 min waiting time between repeat measurements in an individual set) or a short protocol (5 min waiting time). Two technically acceptable results of TLCO were used to derive a mean value for DM and VC for each set of measurements (Transflow, P. K. Morgan, Kent, U.K.). The different sequences of gas mixtures produced no significant differences between the values obtained in ten heart transplant patients for mean TLCO (mmol min-1 kPa-1) (standard first 5.13 +/- 1.15, high-oxygen first 5.14 +/- 1.12; limits of agreement -0.57 to 0.59 for DM or for VC. The long or short protocol produced no significant differences between the means of TLCO (mmol min-1 kPa-1) (long 8.0 +/- 1.9, short 8.0 +/- 1.9; limits of agreement -0.5 to 0.5), DM or VC. This allows the development of a standard test protocol of short duration (about 40 min) making it practical for clinical use without compromising the precision or reproducibility of the results obtained.     

Pearson's fetal movement count (FMC) and antepartum fetal heart rate testing (AFHRT) for antepartum fetal well-being

To evaluate the accuracy of Pearson's fetal movement count (FMC) and antepartum fetal heart rate testing (AFHRT) in 380 high risk pregnancies at Rajavithi Hospital in 1994, the result of the 4 test FMC, AFHRT, FMC + AFHRT (serial test), and FMC + AFHRT (parallel test) were compared in sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false positive rate (FPR), false negative rate (FNR) and accuracy. All tests had equal specificity and FPR. FMC + AFHRT (serial test) had the highest value of sensitivity (66.67%) but lowest value of FNR, NPV and accuracy (33.33%, 40%, 72.73% respectively). PPV was 100 per cent in AFHRT and FMC + AFHRT (serial test). FMC might be used as a first line antepartum fetal well being screening test.     

Relationship between abnormalities on high-resolution CT and pulmonary function in systemic sclerosis

STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.     

Inhibition of nitric oxide synthesis increases adenosine production via an extracellular pathway through activation of protein kinase C

At the time of diagnosis, many sarcoidosis patients have no clinical indication for corticosteroid therapy, and prognostic parameters predicting deterioration are missing. In the present study, we investigated parameters derived from bronchoalveolar lavage (BAL) and serum in 77 patients with recently diagnosed sarcoidosis to test their predictive value. Patients were divided into a group with (Group A, n = 37) and a group without (Group B, n = 40) indications for therapy, and the course of the disease was evaluated after 5.7 +/- 0.4 mo. The CD4+/CD8+ lymphocyte ratio and percentage of BAL lymphocytes were of no predictive value. Release of tumor necrosis factor-alpha (TNF-alpha) from cultured alveolar macrophages (AM) was significantly increased in both groups (Group A = 1,872 +/- 428 pg/ml; Group B = 1,561 +/- 449 pg/ml) as compared with controls (220 +/- 37 pg/ml). In Group B, however, patients with a high level of TNF-alpha release had a significantly greater risk of disease progression than did those with normal TNF-alpha release (43.8% versus 8.3%, respectively). From the serologic parameters investigated, consisting of neopterin, angiotensin converting enzyme (ACE), and soluble interleukin-2 receptor (sIL-2R), only the last was of significant predictive value; 42.1% of sarcoidosis patients in Group B with a high level of sIL-2R experienced disease progression, whereas none of those with a normal level did. We conclude that TNF-alpha release and sIL-2R are suitable parameters for predicting disease progression in sarcoid patients who have no indication for therapy at the time of disease diagnosis.     

Timing and priorities for cystic fibrosis patients candidates to lung transplantation

Bilateral lung transplantation is actually considered a valuable option for patients with endstage lung disease related to cystic fibrosis. Timing is crucial to transplant successfully as many patients as possible and it is mainly based on the progressive worsening of pulmonary function tests and quality of life. We reviewed the charts of all patients accepted for lung transplantation at our institution, in order to assess the role of several functional and demographic parameters; we compared the group of patients able to successfully wait for transplantation (Group A) with patients dying on the waiting list (Group B). Twenty-eight patients were accepted: 15 were successfully transplanted (2 at other institutions) (mean waiting time: 117 days), 7 died waiting (mean waiting time: 108 days) and 6 are still on the list. We recorded FEV-1, FVC, PaO2, PaCO2, supplemental O2 requirement, 6-minute walking test, right ventricular ejection fraction (RVEF) and cardio-pulmonary hemodynamics measured at right heart catheterization; we recorded also age at time of diagnosis and at time of evaluation, sex, weight and Schwachman score. These parameters were compared between Group A and B. Age at time of evaluation, sex, weight and Schwachman score did not present any difference between the two groups, as well as pulmonary function tests, PaO2, 6-minute walk test and RVEF. A statistically significant difference was found in terms of PaCO2 (43.9 +/- 9.3 in Group A vs 69.1 +/- 32.4 in Group B, heart rate at rest (102 +/- 21 vs 131 +/- 12) mean pulmonary artery pressure (20.6 +/- 2.9 vs 36 +/- 15.7), pulmonary vascular resistances (350 +/- 96 vs 460 +/- 119.4), cardiac index (3.2 +/- 0.6 vs 5.4 +/- 0.9). On the base of our initial experience we conclude that a careful evaluation of CF candidates for lung transplantation is recommended. A deterioration of pulmonary function tests and quality of life are useful parameters to accept patients in the waiting list; however priority should be attributed also on the base of cardio-pulmonary hemodynamics. A larger series of patients is required to draw definitive conclusions.     

Pulmonary involvement in polymyositis and in dermatomyositis

OBJECTIVE: To assess prevalence, characteristics, and predictive factors of pulmonary involvement in polymyositis (PM) and dermatomyositis (DM). METHODS: The medical records of 55 consecutive patients with PM and DM between 1983 and 1996 were reviewed. The criteria for diagnosis of PM and DM were based upon Bohan and Peter criteria. RESULTS: Twenty-two patients (40%) developed lung impairment with a mean of 17 months after onset of PM and DM. The 3 main types of pulmonary disorders were interstitial lung disease (41%), ventilatory insufficiency with bronchopneumonia (22.8%), and alveolitis (with pulmonary function tests revealing restrictive pattern, low diffusing capacity, and normal computerized tomography) (36.2%). Both morbidity and mortality rates were as high as 40 and 27%, respectively, in PM and DM patients with lung involvement. Moreover, for the group with pulmonary diseases, serum GOT and ferritin levels were higher (p = 0.01 and p = 0.02) and the presence of anti-Jo-1 antibody and characteristic microangiopathy were more frequent (p < 0.05 and p = 0.0002). CONCLUSION: This series reveals both high prevalence (40%) and severity of pulmonary involvement in PM and DM. Our findings also suggest that high serum GOT and ferritin levels, presence of anti-Jo-1 antibody and characteristic microangiopathy may have predictive value and should encourage the search for pulmonary dysfunction and interstitial lung disease in patients with PM and DM.     

Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema

The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age) were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group (p < 0.01). Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/- 1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05) pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054) after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period. Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations. The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung, and also by directly affecting the proteinase/antiproteinase balance, in favor of antiproteinases, within lung secretions.     

Right ventricular ejection fraction in the preoperative risk evaluation of candidates for pulmonary resection

The major determinants of postoperative morbidity and mortality after lung resection are the physiologic and functional statuses of the pulmonary and cardiac systems. In our previous study, serial measurements of right ventricular performance after pulmonary resection demonstrated significant right ventricular dysfunction in the postoperative period. This study evaluates the preoperative measurement of right ventricular ejection fraction as a predictor of postoperative complications. In addition to conventional cardiopulmonary functional tests, right ventricular function was assessed with a thermodilution technique at rest and during exercise in 18 patients before and 3 weeks after lobectomy or pneumonectomy. The patients were grouped according to severity of right ventricular functional defect: right ventricular ejection fraction of at least 45% (group Ia, n = 8), right ventricular ejection fraction less than 45% (group Ib, n = 10), exercise-induced increases in right ventricular ejection fraction (group IIa, n = 8), and exercise-induced decreases in right ventricular ejection fraction (group IIb, n = 10). Postoperative cardiopulmonary morbidity was recorded for two patients (25%) in group Ia, three patients (30%) in group Ib, no patients (0%) in group IIa, and five patients (50%) in group IIb. Postoperative hospital stay was 28.9 +/- 8.5 days in group Ia, 29.9 +/- 20.2 days in group Ib, 19.4 +/- 8.0 days in group IIa, and 37.5 +/- 15.9 days in group IIb (p < 0.05, group IIa vs group IIb). Although resection-induced changes in forced expiratory volume in 1 second did not differ significantly between group Ia and group Ib, these values appeared to be increased in groups IIa (not statistically significant) and IIb (significantly, p < 0.05). The measured postoperative values of forced expiratory volume in 1 second and vital capacity were significantly higher than the predicted postoperative values (p < 0.05) in group IIa, but not in groups Ia, Ib, and IIb. We conclude that evaluation of right ventricular performance is useful in determining which patients are at increased risk for medical complications after lung resection. Exercise-induced change in right ventricular ejection fraction may be a better indicator of high risk among candidates for pulmonary resection than the absolute value of this parameter.