HERMES: good reasons for harmonising education and training in respiratory medicine.
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Education, Medical, Graduate↗
Biomedical subjects
P L Haslam
Publications and source records attributed to P L Haslam.
BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.
Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking and treatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.
Bronchoalveolar Lavage↗
G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome.
Activated neutrophils play a major role in the pathogenesis of acute respiratory distress syndrome (ARDS), and persistence of pulmonary neutrophilia is related to poor survival. Interleukin (IL)-8 is implicated in recruiting neutrophils to the lungs but it has been postulated that granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), which can promote the survival of neutrophils by delaying apoptosis, may prolong the inflammatory response. The aim of this study was to investigate the levels of GM-CSF and G-CSF in the lungs of patients with ARDS and determine their relationship relative to IL-8 with levels of neutrophils and clinical outcome. The lungs of 31 patients with ARDS were sampled by means of bronchoalveolar lavage (BAL) and assays of the three cytokines were conducted via enzyme-linked immunosorbent assay. GM-CSF, G-CSF and IL-8 were all increased in the patients compared to healthy controls but concentrations of GM-CSF were much lower than those of G-CSF and IL-8 (GM-CSF<G-CSF<IL-8). Levels of G-CSF and IL-8, but not GM-CSF, correlated strongly with each other (rS=0.86, p<0.001) and with BAL neutrophil counts, and only levels of G-CSF were significantly higher in nonsurvivors than survivors (p<0.05). This evidence indicates that granulocyte colony-stimulating factor as well as interleukin-8 plays a role in the mechanisms of pulmonary neutrophilia in acute respiratory distress syndrome, whereas the role of granulocyte-macrophage colony-stimulating factor remains unclear. The higher levels of granulocyte colony-stimulating factor in nonsurvivors, together with previous reports that recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor occasionally induce acute lung injury, emphasize that the role of these mediators in pathogenesis needs to be elucidated.
Adolescent↗
Measurement of ceruloplasmin in the lungs of patients with acute respiratory distress syndrome: is plasma or local production the major source?
BACKGROUND: Oxidant-induced tissue damage is thought to contribute to the lung injury seen in patients with acute respiratory distress syndrome (ARDS). Ceruloplasmin (CP) is a major circulating antioxidant, increased levels of which have been measured in bronchoalveolar lavage fluid (BALF) taken from such patients. Traditionally, CP detected in these circumstances was thought to be plasma-derived, moving into the alveolar spaces as a consequence of the increased alveolar-capillary permeability that characterises ARDS. However, recent studies in murine models suggest that CP may be synthesised in the airways and even alveoli under physiological conditions. OBJECTIVES: The aims of this investigation were therefore to identify the source of any increased levels of CP detectable in BALF taken from patients with established ARDS. METHODS: Matched BALF and plasma samples taken from patients with ARDS (n = 46) and from controls without lung disease (n = 11) were analysed for CP (132 kD) and plasma specific albumin (ALB, 68 kD) and (alpha(2)-macroglobulin (alpha(2)-M, 820 kD). RESULTS: All three proteins were increased in BALF taken from patients with ARDS compared to controls (p < 0.01, ALB and CP; p < 0.001, alpha(2)-M). When protein levels were expressed as the ratios of BALF: plasma (designated Q), Q(CP) and Q(alpha2)-M increased in parallel to Q(ALB) (p < 0.001), indicating that all increases were primarily plasma-derived. Their relative coefficients of excretion (RCE: Q(CP)/Q(ALB) and Q(alpha2)-M/Q(ALB)) demonstrated that the larger molecular weight protein, alpha(2)-M, gave the best discrimination between patients with ARDS and normal controls (0.85 vs. 0.04; p < 0. 01), indicating that this was the most sensitive marker of alveolar-capillary permeability. CONCLUSIONS: Increased levels of CP in BALF from patients with ARDS are mainly attributable to plasma exudation.
Adult↗
Damage to surfactant-specific protein in acute respiratory distress syndrome.
BACKGROUND: Acute respiratory distress syndrome (ARDS) develops in association with many serious medical disorders. Mortality is at least 40%, and there is no specific therapy. A massive influx of activated neutrophils, which damage pulmonary vascular endothelium and alveolar epithelium, leads to alveolar oedema and pulmonary surfactant dysfunction. In-vitro studies show that neutrophil elastase can cleave surfactant-specific proteins and impair surfactant function. If this happens in vivo in ARDS, the response to surfactant therapy will be limited. METHODS: Samples of pulmonary surfactant were obtained from the lungs of 18 patients with ARDS and six healthy controls by bronchoalveolar lavage. We separated proteins in these samples according to molecular weight by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). We then used western blotting with monoclonal antibody E8 to detect the major surfactant-specific protein A (SP-A). FINDINGS: By contrast with controls, 14 of 18 patients had evidence of in-vivo damage to SP-A that resembled damage caused to SP-A when it is cleaved by neutrophil elastase. Controls showed a single band of normal dimers at 66 kDa, whereas 14 of 18 patients showed multiple bands at 66 kDa, 55 kDA, and 30-36 kDa, and six showed additional bands at 36-40 kDa. INTERPRETATION: Direct damage to surfactant-specific proteins occurs in lungs of patients with ARDS, probably by proteolysis. Trials of protein-containing therapeutic surfactant are in progress in ARDS, and our results indicate that the frequent failure to maintain response may result from continuing damage to surfactant by products of activated neutrophils. A combination of surfactant and antiprotease therapy may improve therapeutic prospects.
Adolescent↗
Report of ERS Task Force: guidelines for measurement of acellular components and standardization of BAL.
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Biomarkers↗
Compositional, structural, and functional alterations in pulmonary surfactant in surgical patients after the early onset of systemic inflammatory response syndrome or sepsis.
OBJECTIVES: Sepsis is one of the most important predisposing factors for the development of the acute respiratory distress syndrome (ARDS). Alterations of pulmonary surfactant contribute in the pathogenesis of ARDS. However, little is known about surfactant in patients with less severe grades of lung injury related to sepsis or systemic inflammatory response syndrome (SIRS). Therefore, the purpose of this study was to characterize endogenous surfactant in surgical intensive care patients with sepsis or SIRS. DESIGN: Prospective, observational study. SETTING: University-affiliated, interdisciplinary intensive care unit. PATIENTS: Eleven patients after major surgery with SIRS or sepsis included within 12 hrs of onset and 11 controls without infection or lung disease. INTERVENTIONS: Operating room and standard intensive care unit management. MEASUREMENTS AND MAIN RESULTS: Four serial bronchoalveolar lavage samples (BAL) were recovered over 7 days from the patients and single BAL samples were obtained from controls. BAL cells, total protein, surfactant-associated protein A (SP-A), surfactant alveolar transition forms, and surface activity were analyzed. Two of 11 patients met criteria for acute lung injury and six of the 11 patients met ARDS consensus conference criteria but acute lung injury or ARDS was not persistent. The mean Pao2/F(IO)2 for the patients over 7 days was 253.2+/-15.1 (SEM) and Murray's lung injury score was 1.12+/-0.12, indicating mild-to-moderate lung injury. BAL neutrophil counts were increased (p< .01), and the ratio of poorly functioning light aggregate surfactant to superiorly functioning heavy aggregate surfactant was increased compared with controls (0.32+/-0.06 vs. 0.09+/-0.01, p < .05). SP-A was decreased (1.9+/-0.4 vs. 3.5+/-0.6 microg/mL of BAL, p< .05) and there were increases in the ratios of phospholipid to SP-A (p < .05), protein to SP.A (p < .01), and protein to phospholipid (p < .05). The surface tension-lowering ability of purified heavy aggregate surfactant was significantly impaired (15.6+/-1.6 vs. 2.8+/-0.6 milliNewtons/m, p< .05). CONCLUSIONS: These observations show that surgical patients with SIRS or sepsis who have mild-to-moderate lung injury develop surfactant dysfunction detectable within 7 days of onset. We propose, therefore, that therapeutic strategies to modulate these severe surfactant abnormalities should be considered, as these strategies may have the potential to reduce lung injury, which is associated with a high mortality in sepsis.
APACHE↗
Bronchoalveolar lavage cellularity: lone cryptogenic fibrosing alveolitis compared with the fibrosing alveolitis of systemic sclerosis.
Lone cryptogenic fibrosing alveolitis (CFA) is histologically identical to fibrosing alveolitis associated with systemic sclerosis (FASSc), but it has a much worse prognosis after matching for disease severity at presentation. The aims of this study were to gain insights into possible pathogenetic mechanisms contributing to this prognostic difference, by comparing bronchoalveolar lavage (BAL) cellularity in the two diseases, and to evaluate the relationships between BAL findings and the regional and global extent of disease, quantified by thin-section computed tomography (CT) and lung function indices. Patients with CFA were distinguished by more extensive fibrosing alveolitis on CT (p < 0.02) and by higher counts of neutrophils (total per ml, p < 0.02; percentage p < 0.03) and eosinophils (total per ml, p < 0.002; percentages, p < 0.02) in BAL fluid. After adjustment for functional and morphologic measures of disease extent, eosinophil percentages and total counts were increased in CFA (p < 0.05 in all 12 multivariate models), but they were not independently related to regional or global disease severity. Neutrophil percentages and total counts were virtually identical in CFA and FASSc in disease of comparable severity, and they increased with increasingly extensive lobar disease and global disease, as judged by CT, p < 0.0005 in all analyses. Neutrophil levels were more closely linked to the extent of disease on CT than to the severity of functional impairment, on univariate and multivariate analysis. The higher BAL eosinophil levels seen in CFA, compared with those seen in FASSc, after adjustment for disease extent, indicate that an eosinophilic influx may be linked to the pathogenesis of fibrosing alveolitis. By contrast, BAL neutrophil levels increase with increasingly extensive disease on CT, but they do not differ independently between CFA and FASSc, suggesting that neutrophil degradation products are unlikely to account for the excess mortality in CFA, compared with that in FASSc.
Bronchoalveolar Lavage Fluid↗
Pulmonary surfactant composition early in development of acute lung injury after cardiopulmonary bypass: prophylactic use of surfactant therapy.
Cardiopulmonary bypass surgery (CPB) causes lung injury and at least 2% of adult patients and more children develop the most severe from acute respiratory distress syndrome (ARDS). Pulmonary surfactant deficiency contributes to the pathogenesis of ARDS. It has been proposed that surfactant therapy immediately after CPB might arrest progression to ARDS. However, many patients develop only mild lung injury after CPB. Thus early markers are needed to identify those patients at highest risk to guide selection for treatment. The aim of this study was to determine whether changes in surfactant phospholipids occur, and reflect severity of lung injury within the first few hours after bypass. Because of the relatively low incidence of ARDS in adult patients, this study was conducted using young pigs highly susceptible to bypass-induced lung injury. Eight pigs were given 2 hours bypass. Six controls underwent 'sham' bypass. At 3 h after bypass pulmonary vascular endothelial permeability was assessed by transcapillary leakage of radiolabelled transferrin. A 4 hour broncho-alveolar lavage (BAL) was used to assess intra-alveolar levels of surfactant, inflammatory cells and oedema protein. Bypass caused falls in arterial oxygenation and lung compliance (P < 0.01), but at this early stage in progression of lung injury BAL surfactant phospholipid and albumin levels were within the control range indicating that the alveolar epithelium had not yet suffered major damage. The main abnormalities were increases in vascular endothelial permeability (P < 0.01), BAL neutrophils (P < 0.01), total protein and sphingomyelin (SM) (P < 0.05). Lung histology showed that the main damage was interstitial oedema located around the bronchioles and their associated vessels. A single instilled dose of surfactant phospholipids in 5 animals caused excess in vivo supplementation and did not reduce the early pathophysiologic changes. Our findings suggest that surfactant phospholipid deficiency does not make a major contribution in the initial stages of lung injury after CPB, and that excessive phospholipid supplementation at this stage can be deleterious.
Animals↗
The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability.
STUDY OBJECTIVE: To quantify simultaneously the pulmonary and gastrointestinal (GI) damage that occurs during uncomplicated surgery requiring cardiopulmonary bypass (CPB), and to examine the relationships between markers of such damage. DESIGN: Prospective, open. SETTING: Adult ICU of a national referral hospital. PATIENTS: Twenty patients undergoing elective CPB surgery. MEASUREMENTS AND RESULTS: Pulmonary vascular injury was assessed using the protein accumulation index (PAI), a double isotope technique specific for high permeability pulmonary edema. The relationships of the PAI with percent neutrophils in bronchoalveolar lavage (BAL), serum, and BAL myeloperoxidase (MPO), and bypass time were examined. Splanchnic vascular injury was assessed using tonometry to measure intramucosal pH (pHi) and the ratio of absorbed lactulose to L-rhamnose (L/R ratio) to determine gut mucosal permeability. Positive correlations were observed between bypass time and PAI (r = 0.64, p < 0.01), percent neutrophils in the postoperative BAL and PAI (r = 0.51, p < 0.05), and postoperative serum MPO and PAI (r = 0.77, p < 0.001). The L/R ratio rose significantly following CPB from 0.04 +/- 0.01 in controls to 0.48 +/- 0.05 (p < 0.0001). The L/R ratio in patients who developed a low pHi was 0.59 +/- 0.06 compared with 0.32 +/- 0.07 in those whose pHi remained normal (p < 0.05). No significant correlation between bypass time and pHi (r = -0.3, p = 0.33), bypass time and L/R ratio (r = 0.27, p = 0.26), PAI and L/R ratio (r = 0.2, p = 0.42), PAI and pHi (r = -0.34, p = 0.16), postoperative serum MPO and L/R ratio (r = 0.03, p = 0.90), or postoperative serum MPO and pHi (r = -0.10, p = 0.67) could be demonstrated. CONCLUSIONS: Pulmonary and GI injury are detectable following uncomplicated CPB. The absence of any relationship between the respective markers of dysfunction suggests that differing pathologic processes are responsible.
Aortic Valve↗
Surfactant replacement therapy in late-stage adult respiratory distress syndrome.
In four adult patients with late-stage acute respiratory distress syndrome (ARDS), a single dose of the artificial surfactant ALEC was given by intrabronchial instillation. There was no sustained clinical improvement, but bronchoalveolar lavage measurements indicated that phosphatidylcholine (PC) at 24 h after treatment had increased up to 4.4 fold and phosphatidylglycerol up to 34.7 fold. However, PC relative to total phospholipid remained below normal, and protein contamination relative to PC remained above normal. Thus, therapeutic formulations and regimens to achieve greater and more sustained supplementation of PC may be required in patients with late-stage ARDS.
Adolescent↗
Bronchoalveolar lavage studies of pulmonary surfactant.
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Adult↗
Fibrosing alveolitis in systemic sclerosis. Bronchoalveolar lavage findings in relation to computed tomographic appearance.
Fibrosing alveolitis in systemic sclerosis is histologically identical to lone cryptogenic fibrosing alveolitis (CFA) (idiopathic pulmonary fibrosis). The inflammatory cell content of bronchoalveolar lavage (BAL) samples has been used as a guide to prognosis and treatment in CFA. In this study, the relationship was explored between BAL findings and the extent and pattern of disease within the lavaged lobe, as judged by thin-section computed tomography (CT), in systemic sclerosis. Thirty-eight nonsmoking patients were studied; none had been treated with corticosteroids or immunosuppressive agents, and 11 had no evidence of fibrosing alveolitis on CT. BAL neutrophils were markedly increased in association with extensive disease on CT compared with less extensive disease (p < 0.001) and normal appearances (p < 0.001); the extent of a reticular pattern on CT (denoting fibrosis) correlated with the neutrophil percentage count (p < 0.005) and total neutrophil count/ml (p < 0.01). BAL eosinophils were increased in less extensive as well as in extensive disease when compared with lobes with a normal CT appearance (p < 0.01); eosinophil percentage counts but not total eosinophil counts/ml correlated with the extent of a ground-glass pattern on CT (through to denote inflammation) (p < 0.05). These findings indicate that in systemic sclerosis a BAL neutrophilia is generally associated with extensive fibrotic disease, whereas a BAL eosinophilia is often seen in less advanced disease, particularly when CT appearances suggest lung inflammation.
Bronchoalveolar Lavage Fluid↗
Pulmonary endothelial permeability in patients with severe lung injury. Clinical correlates and natural history.
STUDY OBJECTIVE: To establish the natural history of lung injury in adult respiratory distress syndrome (ARDS) in terms of increased pulmonary vascular permeability. Secondly, to relate such changes to the number of neutrophils in bronchoalveolar lavage (BAL) and a clinical score of the severity of lung injury. DESIGN: Prospective, open. SETTING: Adult intensive care unit of a tertiary (national) referral hospital. PATIENTS: Fourteen patients meeting accepted diagnostic criteria for ARDS. INTERVENTIONS: Mechanical ventilatory support. Conventional intensive care and support for other failed organ systems as appropriate. MEASUREMENTS AND RESULTS: Pulmonary vascular permeability was estimated using a dual isotope technique (protein accumulation index [PAI]), neutrophil numbers by BAL and the severity of ARDS by the lung injury score (LIS). The PAI and LIS were measured simultaneously on three occasions as far apart as possible during the course of the illness. A single BAL was performed immediately after one of the three PAI/LIS measurements, the precise timing being dictated by the clinical stability of each patient. Fourteen patients (8 male; age range, 19 to 69 years) were studied, 1.40 +/- 0.16, 11.36 +/- 1.79, and 20.90 +/- 2.30 days after the onset of ARDS (mean +/- SEM). Six patients died. The PAI (normal range, 0 to 1.0 x 10(-3)) was 2.81 +/- 0.39, 2.94 +/- 0.48, and 2.80 +/- 0.87; and LIS (severe injury > or = 2.5) was 2.18 +/- 0.25, 2.48 +/- 0.14, and 2.06 +/- 0.27, respectively. The BAL neutrophil content was 54.09 +/- 8.89. There were significant positive correlations between PAI and LIS (r = 0.73, p < 0.001) and PAI and BAL neutrophil content (r = 0.81, p < 0.001). CONCLUSIONS: These data suggest that increased pulmonary vascular permeability persists throughout the course of ARDS and is related to a clinical score of injury severity and BAL neutrophil content.
Adult↗
Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis.
Extrinsic allergic alveolitis (EAA) (synonym: hypersensitivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocytic infiltrates in the pulmonary interstitial tissues. We have previously reported that the numbers of lymphocytes in bronchoalveolar lavage (BAL) samples in this disease correlate with levels of cholesterol and neutral lipid-laden 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which are known to be essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesterol is capable of enhancing the antigen-presenting function of mononuclear phagocytes by modulating the expression of HLA-D region products. Incubation of purified monocytes from healthy volunteers with cholesterol in serum-free medium induced a significant increase in both the percentages of monocytes expressing HLA-DQ (P less than 0.02) and in the intensity of expression of the three HLA-D sub-region products, HLA-DQ, -DP and -DR (P less than 0.02, less than 0.01, less than 0.05, respectively). The cholesterol pre-incubated monocytes also exhibited enhanced antigen-presenting function (P less than 0.05), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augment antigen presentation by modulating the expression of HLA-D region products on antigen-presenting cells. Apart from EAA, this observation may also have relevance to inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.
Alveolitis, Extrinsic Allergic↗
Induction of lymphocyte proliferation by antigen-pulsed human neutrophils.
We have investigated whether purified antigen-pulsed human neutrophils can induce a proliferative response in purified resting blood lymphocytes. Neutrophils were pulsed with soluble tetanus toxoid (dose range 25-250 Lf/ml) and co-cultured with autologous lymphocytes that had been depleted of MHC class II expressing cells. The antigen-pulsed neutrophils induced an increase of lymphocyte proliferation which was dependent on the antigen dose and the neutrophil/lymphocyte ratios. Neutrophils were less potent than autologous monocytes in stimulating lymphocyte proliferation. Blocking with a monoclonal antibody to a common determinant of the human MHC class II complex failed to reduce the lymphoproliferative effects and allogenic antigen-pulsed neutrophils were also able to elicit lymphocyte proliferation similar to autologous neutrophils. We conclude that antigen-pulsed neutrophils are able to induce lymphocyte proliferation in a non-MHC-restricted fashion.
Antigen-Presenting Cells↗
In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases.
The in vivo role of interferons in the development of fibrosis is not fully understood but it is known that interferons can suppress fibroblast proliferation and collagen synthesis in vitro. We have recently demonstrated that in a group of patients with sarcoidosis having predominant pulmonary involvement, patients with the highest levels of circulating interferon-gamma (IFN-gamma) more frequently resolved on corticosteroids, suggesting that they had a less 'fibrotic' component to their disease. We now report that in two other diseases, where the tendency to develop pulmonary fibrosis is greater than in sarcoidosis, namely cryptogenic fibrosing alveolitis (CFA) and fibrosing alveolitis associated with the systemic connective tissue disease progressive systemic sclerosis (FA + PSS), very few patients have elevations in IFN-gamma in their serum. However, as in sarcoidosis, those with the highest levels responded to corticosteroids (P less than 0.05). Attempts to measure IFN-gamma levels in the lungs, using cell-free bronchoalveolar lavage (BAL) fluid supernatants, were negative in all the study groups, suggesting that these samples may be inadequate for such studies. To investigate whether there might be an intrinsic defect in T lymphocyte function associated with predisposition to fibrosing lung diseases, we then investigated the in vitro production of IFN-gamma by lymphocytes separated from the blood of 18 untreated patients (six with CFA, six with FA + PSS and six with sarcoidosis). IFN-gamma production was impaired in 10 (56%) (two with CFA, four with FA + PSS and four with sarcoidosis). A higher proportion of the fibrosing alveolitis patients (CFA or FA + PSS) with impaired IFN-gamma production have subsequently shown spontaneous lung functional deterioration. These findings suggest that impaired IFN-gamma release might be a potentiating factor in the pathogenesis of these fibrosing lung diseases.
Adult↗
Increased levels of serum interferon-gamma in pulmonary sarcoidosis and relationship with response to corticosteroid therapy.
The aim of this study was to evaluate serum levels of the lymphokine interferon-gamma (IFNg) in patients with chronic pulmonary sarcoidosis, and to investigate its value as a predictive marker of clinical response to corticosteroid therapy. Twenty-five patients and 28 age-matched control subjects were studied. All the patients had parenchymal shadows (Stage II or Stage III) and none had clinical evidence of extrathoracic disease. Before therapy, serum IFNg levels were significantly higher in the patient group (p less than 0.001), and 20 (80%) had values above the normal range. After oral treatment with corticosteroids for a median 13 months (range, 3 to 49 months) the levels decreased significantly (p less than 0.01). However, the falls were less pronounced in patients who had a better outcome in terms of achieving complete radiographic resolution and in those who improved in forced vital capacity by greater than or equal to 10%. The prognostic value of the pretreatment serum IFNg was explored, and a significant relationship was found between higher pretreatment levels and lower grades or radiographic abnormality assessed 3 yr after commencement of treatment (p less than 0.01). In addition, the patients who had cleared completely while receiving steroids and remained in remission had significantly higher pretreatment serum IFNg levels than did those with incomplete resolution of parenchymal shadows or radiographic relapses (p less than 0.05). We conclude that elevated levels of circulating IFNg are detectable in most untreated patients with Stage II/III pulmonary sarcoidosis and that patients with the highest levels appear to have a better chance of achieving complete resolution with corticosteroid therapy.
Adult↗