[Leukemia with eosinophilia and paraneoplastic eosinophilia].
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Child, Preschool↗
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Granulocyte-macrophage colony-stimulating factor and interleukin-5 concentrations in premature neonates with eosinophilia.
OBJECTIVE: Eosinophilia is common among premature neonates, but little is known about the cytokines responsible for influencing its onset in neonates. In adults and transgenic mice, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) influence the development of eosinophilia. We sought to prospectively determine whether these cytokines correlated with the development of eosinophilia in premature infants. STUDY DESIGN: We measured the absolute eosinophil count (AEC) and serial serum concentrations of GM-CSF and IL-5 in premature neonates with eosinophilia. RESULTS: Among 201 premature neonates, 21 had an eosinophil count of > 700/microliter (occurrence, 10.5%). Of these 21 neonates, 4 had mild (700/microliter to 999/microliter), 13 had moderate (1000/microliter to 2999/microliter), and 4 had severe (> 3000/microliter) eosinophilia. No differences in gestational age or age at onset of eosinophilia were observed between the groups, but the duration of eosinophilia was less with mild than with moderate or severe eosinophilia. A total of 20 of the 21 patients had an infection or necrotizing enterocolitis diagnosed within 48 hours of the onset of eosinophilia. In patients with mild and moderate eosinophilia, serial GM-CSF and IL-5 concentrations were below the lowest enzyme-linked immunosorbent assay standard. There was no correlation between AEC and GM-CSF or IL-5 concentration in these infants. However, in one patient with severe eosinophilia, two distinct elevations in IL-5 were noted (34.6 and 46.0 pg/ml); each peak occurred 7 to 8 days before a peak in eosinophil count. CONCLUSION: Eosinophilia is relatively common, and in those neonates with the highest AECs, the duration of eosinophilia can last for > 6 weeks. The majority of cases of eosinophilia occurred in temporal proximity to an infectious illness or necrotizing enterocolitis. Serum concentrations of IL-5 were elevated in only one of our patients with severe eosinophilia.
Biomarkers↗
Eosinophilia detected by automated blood cell counting in ambulatory North American outpatients. Incidence and clinical significance.
OBJECTIVES: To audit a cohort of ambulatory outpatients with eosinophilia detected on automated blood cell counting. Specific objectives included the determination of whether the eosinophilia had been anticipated, the etiology of the eosinophilia, the clinical follow-up and investigations performed on patients with eosinophilia, and the effect of the detection of eosinophilia on patient management and ultimate clinical outcome. DESIGN: A year-long retrospective review of all patients with an absolute eosinophil count of greater than 0.7 x 10(9)/L. SETTING: A large outpatient laboratory system. The patient population was managed by family physicians and specialists. INTERVENTION: Data collection included the results of the hematology profile, the absolute eosinophil count, the clinical situation responsible for the hematologic profile determination, and the probable cause of eosinophilia. Individual physicians were surveyed to determine if discovery of the eosinophilia had changed patient management plan or clinical outcome. PRINCIPAL RESULTS: Out of 195,300 patients who had a hematology profile performed, 225 were found to have an absolute eosinophilia count higher than 0.7 x 10(9)/L. The overall incidence of eosinophilia in the study population was 0.1%. The eosinophilia was not anticipated in 85% of patients. No obvious cause was detected for the eosinophilia in 36% of patients. Various allergic diseases were responsible for the eosinophilia in the majority of the remaining patients. Fewer than 9% of individuals manifested a serious systemic illness or parasitemia. Further clinical follow-up had been performed in 69% of patients. Additional laboratory tests had been ordered in 59% of patients. The laboratory tests most frequently ordered were a repeat hematology profile or stool examinations for ova and parasites. In only two instances did the discovery of the eosinophilia appear to result in a significant change in patient management or ultimate clinical income. CONCLUSION: The vast majority of eosinophilias detected in ambulatory outpatients are associated with allergic processes. An extensive investigation of eosinophilia in ambulatory North American outpatients does not appear to be warranted unless specifically indicated by the results of the history and physical examination.
Adolescent↗
Blood and graft eosinophilia as predictors of rejection in human liver transplantation.
This study attempts to define the relationship of blood and graft eosinophilia to acute hepatic allograft rejection. Sixty liver transplant patients were studied for the first 30 days postoperatively, with daily serum bilirubin and liver enzyme levels, white blood cell counts and differential counts, and biweekly core liver biopsies. Graft eosinophilia was established if 7% or greater of the cells infiltrating the portal triads were eosinophils. Blood eosinophilia is an absolute eosinophil count greater than 500 cells/mm3 occurring on any of the 5 days preceding the day of rejection. Acute rejection was diagnosed when 2 days of hepatic allograft dysfunction occurred with histologic evidence of rejection. The 2nd day of dysfunction with appropriate histologic findings was arbitrarily chosen as the day of rejection. Graft eosinophilia predicted rejection with 92% sensitivity and 98% specificity. Blood eosinophilia occurred on the average on the day of rejection and on the 2 preceding days, while graft eosinophilia occurred on the day of rejection and on 1 preceding day. Blood eosinophilia followed by graft eosinophilia specifically occurred in cases of rejection. Blood eosinophilia not followed by graft eosinophilia was not associated with rejection. Following treatment of rejection with high-dose corticosteroids, blood and graft eosinophil counts decreased markedly. In summary: (1) graft eosinophilia is very sensitive and specific for acute hepatic allograft rejection; (2) blood eosinophilia closely precedes and parallels graft eosinophilia specifically during acute hepatic allograft rejection; and (3) elevated blood and graft eosinophil counts are markedly reduced following treatment of rejection with high-dose corticosteroids.
Eosinophilia↗
T-cell-dependent eosinophilia in the cerebrospinal fluid of the mouse infected with Angiostrongylus cantonensis.
Eosinophilia of the cerebrospinal fluid (CSF) in permissive (rats) and non-permissive (mice) hosts infected with Angiostrongylus cantonensis, and the possible mechanism of the eosinophilia were studied. In three strains of thymic mice (ICR, ddY and BALB/c), the infection provoked a marked CSF eosinophilia starting at around day 12, reaching a peak level at day 20 and maintaining significantly high levels until day 35. In contrast, in athymic nude mice of BALB/c strain the infection failed to evoke this eosinophilia, suggesting T-cell dependence of murine CSF eosinophilia. Humoral antibodies did not correlate with the induction of eosinophilia. A time-course study of worm recovery in the mouse brains indicated a gradual but consistent reduction in worm burden in accordance with the rapid rise in CSF eosinophil levels. Bone marrow eosinophilia occurred in mice at day 5, which preceded CSF eosinophilia. Jirds, a permissive but less susceptible host, developed a CSF eosinophilia with a peak level at day 17, but which declined rapidly following the peak. Permissive rat hosts developed significant peripheral and bone marrow eosinophilia at day 35 but their CSF eosinophilia was markedly less prominent than that of mice and jirds. These data clearly indicate that there are distinct differences in the mechanism of eosinophilia and eosinophilia-inducing factors between permissive and non-permissive hosts.
Angiostrongylus↗
Significance of eosinophilia after stem cell transplantation as a possible prognostic marker for favorable outcome.
Although eosinophilia after stem cell transplantation (SCT) has been addressed in recent reports, the significance of eosinophilia in disease outcome after SCT has not been well studied. In this study, we investigate the frequency of eosinophilia after SCT to determine its prognostic value. The subjects were 113 patients with malignant or nonmalignant diseases who underwent SCT treatment. In these patients, eosinophilia was detected in 44 cases (38.9%), on average 67.5 days after transplantation, and the mean maximum absolute eosinophil count was 840.5 x 10(6)/l. To study the basis of eosinophilia after SCT, various serum cytokine levels during SCT in patients both with and without eosinophilia were analyzed. Statistical analysis indicated that the overall patient survival rates improved in those with eosinophilia compared to those without eosinophilia (88.7 vs 43.0%, P=0.0034). In particular, in patients with malignant diseases, those with eosinophilia showed a higher event-free survival (81.1 vs 44.6%, P=0.0025) and a lower relapse rate (16.0 vs 43.0%, P=0.0287) than those without eosinophilia. In conclusion, we propose that eosinophilia after SCT could be a useful prognostic marker for determining favorable outcomes in patients with malignant diseases. The reasons for this good prognosis in SCT patients with eosinophilia are discussed.
Adolescent↗
Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome.
Hypersensitivity syndrome (HSS) usually refers to severe drug eruption associated with systemic symptoms and eosinophilia. Interleukin (IL)-5 regulates eosinophil counts with the help of IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Blood IL-5 levels have been reported to be increased in patients with eosinophilia secondary to parasitic infections or idiopathic eosinophilia, but have never been evaluated in drug-induced eosinophilia. The aim of our study was to determine whether IL-5, IL-3 and GM-CSF are involved in eosinophilia in patients with drug-induced HSS. Plasma levels of IL-3, IL-5 and GM-CSF were assayed by ELISA in seven patients with drug-induced HSS, in eight patients with cutaneous adverse drug reactions not associated with eosinophilia, and in five patients with eosinophilia unrelated to drug treatment. IL-5 levels were normal in all eight patients with drug eruptions without eosinophilia, and increased in five of the seven patients with HSS. In the latter patients, IL-5 levels peaked several days before highest eosinophil counts were noted, and returned to normal within a few days, even when eosinophilia persisted. In patients with eosinophilia unrelated to drug treatment, IL-5 levels, although significantly increased remained lower than in HSS patients. IL-3 and GM-CSF could not be detected in any group, at any time. Our results show that IL-5 is involved in drug-related eosinophilia. As IL-5 production was only involved in the early stages of the reaction, it is suggested that IL-5 mainly derives from activated lymphocytes rather than eosinophils. Our results support the clinical relevance of previous in vitro findings. Further studies are needed to test whether assays of IL-5 production by lymphocytes of patients stimulated by the suspected drug and/or its metabolites, are useful in establishing causality in drug-induced reactions associated with eosinophilia.
Adult↗
Experimental pulmonary eosinophilia in mice by Ascaris suum extract.
The transnasal administration of an extract of the parasite Ascaris suum (Asc) to C57BL/6 mice for 3 wk produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. This pulmonary eosinophilia was not accompanied by blood eosinophilia. The oral administration of cyclosporin, 50 mg/kg body weight, every other day significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB X C57BL/6)F1-W/WV (W/WV) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of eosinophilia in BAL in this model. C57BL/6, W/WV, and Balb-C mice that developed eosinophilia in the BAL also showed elevated total IgE levels and IgE titers against Asc in the sera. On the other hand, C57BL/6-nu/nu mice and IgE low-responder SJL mice, which developed little eosinophilia, did not show elevated total IgE levels and IgE titers against Asc in the sera. However, oral administration of cyclosporin, 50 mg/kg, which inhibited eosinophilia in the BAL in C57BL/6 mice, did not significantly inhibit the elevation of total IgE or IgE against Asc in the sera. This indicates that serum IgE production is not required for the formation of eosinophilia.
Animals↗
[Transient eosinophilia in primary biliary cirrhosis].
We reviewed 144 differential white blood cell counts from 23 patients with primary biliary cirrhosis (PBC, 21 females, 2 males) for occurrence of eosinophilia. Over an average observation time of 43 +/- 9 months, 9/23 (39%, 9 female) patients were found to have transient absolute (> 500/mm3, n = 5) or relative (> or = 6%, n = 4) blood eosinophilia. The maximum value of eosinophilic granulocytes observed was 1385/mm3 (19%). Other causes of eosinophilia had been ruled out. Eosinophilia was transient, disappearing without treatment. Significantly younger patients with eosinophilia also had a tendency to prognostically more favourable values for serum albumin, prothrombin time, bilirubin and galactose elimination capacity. None had edema, compared to two patients with edema in the group without eosinophilia. Two patients died during the observation period; both were from the group without eosinophilia. The average 5- and 7-year survival probability, calculated on the Mayo survival model, tended to be higher for patients with eosinophilia (92% and 87%) compared to patients without eosinophilia (79% and 72%). In patients with eosinophilia, disease stage I (5/6 vs 1/9) and epitheloid cell granuloma (4/6 vs 1/9) were significantly more frequent. Blood eosinophilia in PBC seems to be an indicator of an early disease state with florid bile duct lesions. Primary biliary cirrhosis should therefore be considered--with other hepatopathies--as a possible cause of eosinophilia of otherwise unknown origin. These observations could be of importance for future therapeutic concepts, at least for patients in early disease states.
Adult↗
Eosinophilia-myalgia syndrome in L-tryptophan-exposed patients.
OBJECTIVES: To study the incidence of eosinophilia-myalgia syndrome, the risk factors associated with the syndrome, and the clinical spectrum of illness associated with L-tryptophan use in an exposed population. DESIGN: Retrospective cohort and nested case-control studies of risk factors for eosinophilia-myalgia syndrome using inpatient and outpatient chart reviews, telephone interviews, and in-person patient interviews. Descriptive study of clinical course of L-tryptophan users. SETTING: Office practice of one psychiatrist based in a small city (population 43,467) in South Carolina. PATIENTS: Eligible subjects were all patients from the practice who used L-tryptophan during the 1989 study interval. Of these, 418 (87%) were interviewed. MAIN OUTCOME MEASURES: Clinical spectrum of illness associated with L-tryptophan use, including definite and possible cases of eosinophilia-myalgia syndrome. RESULTS: Among the 418 interviewed L-tryptophan users, we identified 47 definite cases (11%) and 68 possible cases (16%) of eosinophilia-myalgia syndrome, most of which involved patients who were using one retail brand of L-tryptophan (brand A). Among the 157 brand A users, we identified 45 definite cases (29%) and 36 possible cases (23%) of eosinophilia-myalgia syndrome, and the risk for the syndrome increased as the brand A dose increased. Fifty percent (19 of 38) of those using more than 4000 mg/day developed definite eosinophilia-myalgia syndrome, and 84% (32 of 38) developed either definite or possible eosinophilia-myalgia syndrome. On multivariate analysis, risk for definite eosinophilia-myalgia syndrome was associated with brand A dose and age of the patient; however, gender, race, and use of other medications were not associated with the syndrome. CONCLUSIONS: These results suggest that many people exposed to the agent causing eosinophilia-myalgia syndrome may develop illness, and dose of presumably contaminated L-tryptophan is the single most important predictor of eosinophilia-myalgia syndrome. The broad range of signs and symptoms reported by patients using L-tryptophan illustrates that a strict case definition may identify only about half of those affected.
Adult↗
Eosinophilia in rheumatologic diseases: a prospective study of 1000 cases.
The role of eosinophilia in connective tissue diseases and the relationship between symptoms of rheumatic disease and eosinophilia have not been clearly established. The purpose of the present study was to explore the prevalence of eosinophilia in rheumatologic disease and determine its relationship to the symptoms. One thousand patients who applied to our rheumatology outpatient clinic between 2001 and 2002 were prospectively studied. The upper limit of normal blood eosinophil numbers was determined as 500 cells/microl of blood. A detailed history was obtained from all patients and careful physical examination was done. A negative correlation was observed between eosinophilia and dryness of the mouth, vitiligo, and fatigue (P < 0.05). Nonsteroidal anti-inflammatory drug usage correlated positively with eosinophilia, which was also statistically meaningful (P < 0.05). Twenty-six of our patients with fibromyalgia (n = 293), three of our subjects with rheumatoid arthritis who were using methotrexate (n = 182), 15 of whom who were not on methotrexate therapy, and one of the 26 with vasculitis had eosinophilia, which was not statistically significant (P > 0.05). None of the patients with scleroderma (n = 12) had eosinophilia. Eleven of the patients with gout had eosinophilia, and only one of them was using allopurinol. We conclude that eosinophilia can be seen in various rheumatologic conditions but, as corticosteroids are one of the most common medications used in collagen tissue diseases, the eosinophil numbers found may be lower than expected and eosinophilia may be more frequent than reported.
Adult↗
Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment.
Acquired blood eosinophilia is considered either a primary or a secondary phenomenon. Causes of secondary (ie, reactive) eosinophilia include tissue-invasive parasitosis, allergic or inflammatory conditions, and malignancies in which eosinophils are not considered part of the neoplastic process. Primary eosinophilia is classified operationally into 2 categories: clonal and idiopathic. Clonal eosinophilia stipulates the presence of either cytogenetic evidence or bone marrow histological evidence of an otherwise classified hematologic malignancy such as acute leukemia or a chronic myeloid disorder. Idiopathic eosinophilia is a diagnosis of exclusion (ie, not secondary or clonal). Hypereosinophilic syndrome is a subcategory of idiopathic eosinophilia; diagnosis requires documentation of both sustained eosinophilia (absolute eosinophil count > or = 1500 cells/microL for at least 6 months) and target organ damage (eg, involvement of the heart, lung, skin, or nerve tissue). Genetic mutations involving the platelet-derived growth factor receptor genes (PDGFR-alpha and PDGFR-beta) have been pathogenetically linked to clonal eosinophilia, and their presence predicts treatment response to imatinib. Accordingly, cytogenetic and/or molecular investigations for the presence of an imatinib-sensitive molecular target should accompany current evaluation for primary eosinophilia. In the absence of such a drug target, specific treatment is dictated by the underlying hematologic malignancy in cases of clonal eosinophilia; however, the initial treatment of choice for symptomatic patients with hypereosinophilic syndrome is prednisone and/or interferon alfa.
Benzamides↗
Eosinophilic fasciitis is clinically distinguishable from the eosinophilia-myalgia syndrome and is not associated with L-tryptophan use.
Induration of the skin develops in a majority of patients with the eosinophilia-myalgia syndrome associated with L-tryptophan, and bears striking clinical and histopathological resemblance to eosinophilic fasciitis (EF). These similarities have led to the suggestion that eosinophilia-myalgia syndrome and EF are the same disease. To study the relationship of eosinophilia-myalgia syndrome and EF, we ascertained the prevalence of L-tryptophan use in a cohort of patients with EF, and compared their clinical and laboratory findings to those of patients with eosinophilia-myalgia syndrome associated cutaneous involvement. None of 11 patients who were diagnosed as having EF between 1970 and 1989 used L-tryptophan containing preparations prior to the onset of their illness. Marked clinical and laboratory test differences were observed between patients with EF and eosinophilia-myalgia syndrome. Patients with eosinophilia-myalgia syndrome had a more acute onset, more severe symptoms, higher frequency of rash and of pulmonary, cardiac, gastrointestinal, neurologic, myopathic and thyroid involvement compared to patients with EF. Corticosteroid therapy resulted in improvement of cutaneous involvement in 88% of patients with EF but it was only partially successful in patients with eosinophilia-myalgia syndrome. Hospitalization and fatalities occurred only among patients with eosinophilia-myalgia syndrome. These observations demonstrate that eosinophilia-myalgia syndrome is a more severe disease with multisystemic involvement that can be clinically distinguished from EF. In contrast to eosinophilia-myalgia syndrome, EF is not associated with L-tryptophan ingestion.
Adrenal Cortex Hormones↗
Clinical significance of eosinophilia in HIV-infected individuals.
PURPOSE: To assess the clinical significance of peripheral eosinophilia in HIV-infected individuals. METHODS: In a retrospective case-control study we compared 42 HIV-infected patients (cases) with peripheral eosinophilia (absolute eosinophil count > 500 cells/mm3) with 84 HIV-infected controls without eosinophilia. Cases were matched to controls by date, and by CD4 cell count. Data on clinical parameters possibly associated with eosinophilia were collected and compared among cases and controls. RESULTS: Eosinophilia was seen in patients with late-stage HIV disease (median CD4 cell count of 26 cells/mm3). Cases were more likely to be black (52% versus 18%, P = 0.0001), have pruritus (50% versus 20%, P = 0.002), and have a physician-documented rash (76% versus 52%, P = 0.02). Specific cutaneous diagnoses that were more prevalent in cases versus controls were eosinophilic folliculitis (24% versus 1% P = 0.0001), atopic dermatitis (14% versus 1%, P = 0.01), and prurigo nodularis (7% versus O, P = 0.07). Other parameters commonly associated with eosinophilia such as allergic reactions, parasitic infection, malignancy, and adrenal insufficiency were not found at higher incidence in cases. CONCLUSIONS: Eosinophilia in AIDS patients is associated with cutaneous disease, but not with other conditions commonly associated with eosinophilia including parasitic infections, allergic reactions, or malignancy. Extensive work up for asymptomatic eosinophilia in patients with AIDS and cutaneous disease is not warranted.
Adult↗
Biopsy eosinophilia as a predictor of renal graft dysfunction.
AIM: The aim of this research was to assess the impact of eosinophilia in renal biopsy specimens obtained during an acute rejection (AR) episode on the severity and reversibility of rejection and on long-term graft function. MATERIAL: Among 165 renal graft recipients who underwent transplantation (Tx) in 2001 and 2002 whose biopsy specimens revealed AR, 49 with tissue eosinophilia were compared with control group of 48 without this feature. The average biopsy time was 60.6 and 95.8 days, respectively. Biopsies during delayed graft function were performed in 46.9% of patients with eosinophilia and 29% in the control group. The immunosuppressive regimen was based on tacrolimus or cyclosporine. RESULTS: Tissue eosinophilia was observed in 49 of 165 patients (29.6%): 5 patients had eosinophilia <10/mm(2), 31 patients 10-100/mm(2), 13 patients >100mm(2) (3 patients >300/mm(2)). Severity of AR according to Banff score was statistically lower in the control group (P <.002). Patients with tissue eosinophilia who initially received steroid-free treatment presented with significantly higher (P =.02) biopsy/patients index (2.3 vs 1.81) than the total eosinophilic group. Serum creatinine values at 6 and 12 months after transplantation (Tx) were higher among eosinophilic when compared with the control group (2.41 vs 1.82 mg/dL, P <.002; 2.10 vs 1.98 mg/dL, P =.006, respectively). Chronic rejection within the first year occurred in 25% of patients with tissue eosinophilia, and 8.3% of patients in the control group. One-year graft survival rate among patients with tissue eosinophilia was lower compared with the control group (89.8% and 93.7%, respectively). CONCLUSIONS: Biopsy eosinophilia is a negative predictor that indicates a more severe course of AR and a worse response to treatment with the threat of chronic graft dysfunction.
Biopsy↗
Frequency, levels, and significance of blood eosinophilia in systemic sclerosis, localized scleroderma, and eosinophilic fasciitis.
Blood eosinophilia is a common feature of eosinophilic fasciitis and is variably reported in systemic sclerosis and localized scleroderma. Since these diseases share cutaneous fibrosis as the final outcome and have other clinical and pathologic features that are difficult to differentiate, the presence of blood eosinophilia may be a further source of confusion. In this study, we examined the frequency and level of blood eosinophilia in 715 patients with systemic sclerosis, 72 patients with localized scleroderma, and 22 patients with clinically active eosinophilic fasciitis. When defined as greater than 400 cells/mm3, eosinophilia was present in 7% of patients with systemic sclerosis, 31% of patients with localized scleroderma, and 83% of patients with eosinophilic fasciitis. Greater than 1000 eosinophils/mm3 were present less frequently in systemic sclerosis (1%) and localized scleroderma (8%) than in eosinophilic fasciitis (61%). No difference in the frequency of eosinophilia was present in patients with the limited cutaneous CREST syndrome or the diffuse cutaneous variety of systemic sclerosis, and in these patients the presence of eosinophilia did not correlate with the extent of cutaneous or internal organ involvement or with other laboratory abnormalities. Among patients with localized scleroderma, eosinophilia was more common in those with linear scleroderma and generalized morphea than in those with morphea, and both the frequency and level of eosinophilia were greater in individuals with clinically active disease (p less than 0.02). Eosinophilia was a persistent feature in untreated patients with active eosinophilic fasciitis, even up to 30 months of disease duration.
Eosinophilia↗
Smoking and atopy as determinants of sputum eosinophilia and bronchial hyper-responsiveness in adults with normal lung function.
Data concerning the determinants of sputum eosinophilia and bronchial hyper-responsiveness (BHR) in large cohorts of individuals with normal lung function are limited. Here, we assessed the occurrence of sputum eosinophilia and BHR and identified the risk factors for these variables in two populations living in North Karelia, Finland, and in Pitkäranta, the Republic of Karelia, Russia. These areas are geographically adjacent, but differ, however, fundamentally in major cultural, socioeconomical and lifestyle aspects. The study population comprised 790 Finns and 387 Russian, aged 25-54 years, who were randomly enrolled from the population registers. A methacholine challenge test to measure BHR was successfully performed in 581 (74%) Finns and 307 (79%) Russians with virtually normal lung function (FEV1 > 70% of predicted). Of these, induced sputum samples were obtained from 41% of the Finns and from 67% of the Russians. The proportion of current smokers was 27% among the former and 42% among the latter. Sputum eosinophilia was assessed using a semi-quantitative method, and total concentrations of sputum eosinophilic cationic protein (ECP) and myeloperoxidase (MPO) were measured using an immunoassay. Risk factors for BHR and sputum eosinophilia were identified with a regression analysis. The prevalence of sputum eosinophilia was 22% among the Finns and 19% among the Russians, and the respective figures for BHR were 14% and 13%. The median ECP concentration in sputum was significantly higher among the Russians as compared with the Finns (P<0.001), whereas for MPO, the difference did not achieve significance. Current smoking was significantly associated with both sputum eosinophilia and BHR in Russia (OR 3.1, 95% CI 1.2-7.6 for sputum eosinophilia, 2.8, 1.3-6.1 for BHR) and with BHR in Finland (2.1, 1.3-3.7). Atopy showed a tendency to be another risk factor for BHR in Finland (1.6, 0.98-2.6). In conclusion, sputum eosinophilia and BHR occurred commonly among the Finns and the Russians with normal lung function. Current smoking was significantly associated with BHR in both countries and additionally with sputum eosinophilia in Russia. Atopy was identified as a risk factor, albeit of borderline significance, for BHR in Finland only, suggesting that there may be differences in the aetiology and nature of BHR between the two countries.
Adult↗
The effects of drugs on Sephadex-induced eosinophilia and lung hyper-responsiveness in the rat.
1. Rats given an intravenous injection of Sephadex particles (0.5 mg of G200 in 1 ml of saline) on days 0, 2 and 5 had a blood eosinophilia which was maximal on day 7. 2. On day 7, broncho-alveolar lavage (BAL) fluids taken from the rats contained an increased number of eosinophils and fewer mononuclear cells but there was no change in the small number of neutrophils. In addition the rats were hyper-sensitive to the increase in resistance to artificial respiration produced by 5-hydroxytryptamine (5-HT), given intravenously, with a shift to the left of the log dose-response curve. Lung parenchymal strips, taken from the rats on days 6, 7 and 8, were hyper-reactive to 5-HT with an increase in slope of the log dose-response curve. 3. Compounds with a wide variety of activities were evaluated for their effects on the blood eosinophilia on day 7 when given before each injection of Sephadex. The eosinophilia was reduced by glucocorticosteroids, beta-adrenoceptor agonists, aminophylline, dapsone and phenidone. 4. Dexamethasone, isoprenaline, dapsone and phenidone at doses that reduced the blood eosinophilia also reduced the changes in number of leucocytes in the BAL fluids and the hyper-responsiveness to 5-HT in vivo and in vitro, except that the effects of dapsone on the hyper-sensitivity to 5-HT in vivo did not reach significance. Aminophylline was the least effective of the drugs at reducing the blood eosinophilia and its effects on the other changes did not reach significance. Sodium cromoglycate reduced the BAL eosinophilia but had no effect on the other changes produced by Sephadex. 5. The correlation coefficients between blood eosinophil numbers and reactivity to 5-HT in vitro and sensitivity in vivo were r = 0.76, (n = 88; P < 0.001) and r = 0.53, (n = 61; P < 0.001) respectively. 6. Doses of dexamethasone, isoprenaline, dapsone and phenidone that reduced the blood eosinophilia when given before each injection of Sephadex were inactive when given up to 8 h after the Sephadex. 7. These data show an association between blood eosinophilia and hyper-responsiveness of the lung. The blood eosinophilia in the rats was triggered within the first few hours of injecting the Sephadex and drugs have been identified which inhibit this trigger.
Animals↗