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PubMed1998

Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis.

A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment. Clinical measurements were made blind to the laboratory findings and vice-versa. Eighteen of 20 patients completed the study. Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia. Only in patients with sputum eosinophilia did prednisone, as compared with placebo, produce a statistically significant and clinically important mean effect on effort dyspnea of 0.8 (95% confidence interval [CI]: 0.3 to 1.2), p = 0.008, and in quality of life of 1.96 (95% CI: 0.5 to 3.3), p = 0.01, associated with a small improvement in FEV1 of 0.11 L (95% CI: - 0.04 to 0.23 L), p = 0.05. In these patients, prednisone also produced a significant decline in the median sputum eosinophil percentage, from 9.7% to 0.5% (p = 0.002), eosinophil cationic protein (ECP), from 6, 000 microgram/L to 1,140 microgram/L (p < 0.001), and fibrinogen, from 25. 3 mg/L to 5.4 mg/L (p < 0.001). These findings indicate that in smokers with severe airflow limitation, sputum eosinophilia predicts a beneficial effect of prednisone treatment. Improvement in FEV1, after prednisone treatment in this population, is small, and may not be appreciated in clinical practice.

Adult↗

PubMed1980

Epidemiologic observations on eosinophilia and its relation to respiratory disorders.

The percentage of eosinophils (%EOS), determined from a differential blood smear, was measured in 2,311 subjects enrolled in a general population study in Tucson, Arizona. A subgroup of 290 subjects was tested in more detail during a later evaluation in which absolute eosinophil counts, leukocyte counts, and nasal smears for eosinophils were obtained. In men, but not in women, there was a significant tendency for the %EOS to decrease with age. The highest %EOS was noted during the months of February through May, the time when most plants in this region are in bloom. Blood eosinophils were significantly related to allergy skin test reactivity, circulating IgE concentrations, several respiratory symptoms and disease diagnoses, as well as to reduced ventilatory function. Among subjects younger than 55 yr of age, however, ventilatory function was significantly low, and symptom rates increased only when there was allergy skin test reactivity in addition to eosinophilia. Neither allergy skin test reactivity nor eosinophilia alone was related to ventilatory function in this age group. Among older subjects, blood eosinophilia was associated with definite impairment of ventilatory function, regardless of skin test reactivity and independent of smoking habits. The presence of eosinophilia identified a predominantly female group of elderly nonsmokers with markedly impaired ventilatory function. These subjects appeared to fall into the clinical category of "asthmatic bronchitis".

Adolescent↗

PubMed2006

Airway eosinophilia in children with severe asthma: predictive values of noninvasive tests.

RATIONALE: Children with severe asthma experience persistent symptoms despite maximal conventional treatment. Fraction of exhaled nitric oxide (Fe(NO)) and sputum eosinophils are used as markers of airway inflammation to guide treatment with steroids, but no data are available on how reliable they are in predicting airway eosinophilia assessed bronchoscopically in these children. OBJECTIVES: To determine how Fe(NO) and sputum eosinophils predict airway eosinophilia measured in both bronchoalveolar lavage (BAL) and endobronchial biopsy. METHODS: Twenty-seven children with moderate to severe persistent asthma attempted measurement of Fe(NO) and sputum eosinophils, followed by bronchoscopy, BAL, and endobronchial biopsy within 24 h. MAIN RESULTS: Significant correlations were found between eosinophils in sputum and both BAL eosinophils (n = 20, r = 0.45, p = 0.045) and Fe(NO) (n = 23, r = 0.42, p = 0.049). The relationship between Fe(NO) and BAL eosinophils was also significant with a stronger correlation (n = 24, r = 0.54, p = 0.006). The positive predictive value (PPV) for increased sputum eosinophil percentage (> 2.5%) to detect elevated eosinophils in BAL (> 1.19%) was 75%; the negative predictive value (NPV) was 63%. All patients with both increased sputum eosinophils and an elevated Fe(NO) value (> 23 ppb) had elevated eosinophils in BAL (PPV, 100%); the NPV of these two markers was 65%. Eight of nine patients without any sputum eosinophils had normal subepithelial eosinophil numbers (< 1.2%; NPV, 89%). However, the PPV of any sputum eosinophils for increased subepithelial eosinophilia was only 36.4%. CONCLUSIONS: There was moderate agreement between both Fe(NO) and sputum eosinophils and BAL eosinophils. There was good NPV, but only poor PPV for these markers for mucosal eosinophilia.

Adolescent↗

PubMed2000

Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs.

The characteristic features of bronchial asthma, including airway eosinophilia and elevated immunoglobulin (Ig)E levels, are known to be orchestrated by T-helper (Th) 2 cells. Oligodeoxynucleotides containing CpG motifs (CpG) have recently been highlighted as an immunomodulator that biases toward a Th1-dominant phenotype. However, CpG may incur nonspecific Th1 activation and toxic effects. In this study we report a novel inhibition of Th2 cells by transmucosal inoculation of antigen and CpG. Intratracheal instillation of CpG inhibited airway eosinophilia and Th2 cytokine production in antigen-sensitized mice. The inhibition was observed when CpG was given at the same time or in advance of antigen challenge. Notably, concomitant administration of CpG and antigen (as opposed to either one alone) was essential for the inhibitory effects. The antigen dose could be minimized to avoid a harmful boost of eosinophilia. CpG had few effects on systemic anti-ovalbumin IgE responses. These results demonstrate that a synergism between transmucosally administered allergen and CpG inhibits Th2 cells in parallel with an improvement in airway eosinophilia and hyperresponsiveness without impeding systemic immune responses. Our data imply that inhalation of a minimal amount of allergen plus CpG could be a novel desensitization therapy for patients with bronchial asthma.

Animals↗

PubMed1980

Comparison of human eosinophils from normals and patients with eosinophilia.

Previous studies of the biochemistry and physiology of eosinophils have relied upon cells obtained from patients with eosinophilia (EE). It is unknown whether such cells might have been activated or partially exhausted by the pathological state causing eosinophilia. We examined cell surface charge, membrane transport of deoxyglucose, activation of lyso-somal acid phosphatase, and oxidative metabolism to provide a profile to compare EE with purified normal eosinophils (NE) and normal neutrophils. Eosinophils or neutrophils were obtained in >95% purity from normal individuals and patients with eosinophilia of diverse etiologies. Cell surface charge was determined by electrophoretic mobility in micromoles per second per volt per centimeter. Normal eosinophils demonstrated a surface charge of 2.46+/-0.03. Stimulation of the cells by zymosan-activated serum (ZAS) reduced the surface charge to 1.82+/-0.02. In contrast, the charge of "resting" EE was already reduced (1.89+/-0.05) and was not altered by ZAS. Resting and stimulated neutrophils had a charge of 1.98+/-0.01 and 1.69+/-0.02, respectively. Uptake of [(3)H]2-deoxyglucose has been shown to reflect carrier-facilitated hexose transport in granulocytes. Deoxyglucose uptake by resting NE and NE stimulated by ZAS was 2.40+/-0.40 and 5.44+/-0.39 (cpm x 10(-3)/2 x 10(5) eosinophils), respectively. Resting and stimulated EE demonstrated deoxyglucose uptake of 7.55+/-0.58 and 15.3+/-0.6, respectively.Lysosomal acid phosphatase was determined by an electron microscopic cytochemical technique. In normal eosinophils and neutrophils, lysosomal acid phosphatase in mature cells is held in a latent form. Normal eosinophils demonstrated weakly positive acid phosphatase activity in 7.8+/-1.2% of the specific granules. Normal eosinophils, stimulated by opsonized staphylococci or the calcium ionophore A23187, develop rapid activation of acid phosphatase in approximately 80% of the granules throughout the cells. Resting EE were usually already activated and demonstrated acid phosphatase in 48.6+/-8.6% of the granules (range, 2-95% granules positive; significant activation was observed in preparations in EE from 11 of 15 patients). Oxidative metabolism was monitored by measurement of the hexose monophosphate shunt (HMPS) (metabolism of 1-[(14)C]glucose to (14)CO(2)). Previous studies demonstrated that resting EE have an HMPS activity which is nearly that of stimulated neutrophils, yet EE remain capable of further 7-10-fold increase when stimulated by opsonized zymosan. In contrast, the HMPS of NE (resting and stimulated) was not significantly different from that of neutrophils. Thus eosinophils obtained from patients with eosinophilia appear significantly activated when compared with normal eosinophils by the criteria of surface charge, activation of lysosomal acid phosphatase, membrane hexose transport, and hexose monophosphate shunt activities.

Acid Phosphatase↗

PubMed2004

FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia.

A novel oncogenic mutation (FIP1L1-PDGFRA), which results in a constitutively activated platelet-derived growth factor receptor-alpha (PDGFRA), has been invariably associated with a primary eosinophilic disorder. The current study examines both the prevalence and the associated clinicopathologic features of this mutation in a cohort of 89 adult patients presenting with an absolute eosinophil count (AEC) of higher than 1.5 x 10(9)/L. A fluorescence in situ hybridization (FISH)-based strategy was used to detect FIP1L1-PDGFRA in bone marrow cells. None of 8 patients with reactive eosinophilia displayed the abnormality, whereas the incidence of FIP1L1-PDGFRA in the remaining 81 patients with primary eosinophilia was 14% (11 patients). None (0%) of 57 patients with the hypereosinophilic syndrome (HES) but 10 (56%) of 19 patients with systemic mast cell disease associated with eosinophilia (SMCD-eos) carried the specific mutation. The bone marrow mast cell infiltration pattern in FIP1L1-PDGFRA(+) SMCD-eos was distinctly diffuse with loose tumoral aggregates. Treatment with low-dose imatinib (100 mg/d) produced complete and durable responses in all 8 FIP1L1-PDGFRA(+) cases treated. In contrast, only 40% partial response rate was seen in 10 HES cases. FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant mutation in primary eosinophilia that is indicative of an underlying systemic mastocytosis.

Adolescent↗

PubMed2002

Assessment and evaluation of symptomatic steroid-naive asthmatics without sputum eosinophilia and their response to inhaled corticosteroids.

Eosinophilic airway inflammation is one of the hallmarks of asthma. Sputum eosinophilia has been suggested as a predictor of the response to inhaled corticosteroids in asthma. This study sought to investigate the proportion of steroid-naive uncontrolled asthmatics without significant sputum eosinophilia (< or = 1%) and to examine whether sputum eosinophilia could predict the response to inhaled corticosteroids. A total of 51 mild uncontrolled steroid-naive asthmatics who had not been treated with oral or inhaled corticosteroids for at least 3 months were investigated. The evaluation included a spirometry, methacholine inhalation challenge and sputum induction on two occasions, one at baseline and the other after 1 month of treatment with 250 microg twice-daily fluticasone propionate. Of the 51 subjects, 15 had an eosinophil count < or = 1%, and 46 completed the two visits. Patients with baseline sputum eosinophils < or = 1% (n=14) were compared with those with sputum eosinophils > 1% (n=32). The baseline characteristics of these two groups were similar. After 1 month of treatment, respiratory symptoms, quality of life, forced expiratory volume in one second (FEV1) and provocative concentration causing a 20% fall in FEV1 improved in both groups. The absence of sputum eosinophilia does not seem to be an indicator of poor response to inhaled corticosteroid treatment in steroid-naive asthmatics. However, this finding needs to be investigated further in a double-blind, placebo-controlled study, entirely designed to answer this question.

Administration, Inhalation↗

PubMed2001

Systemic and eosinophilic lesions in rats with spontaneous eosinophilia (mes rats).

The mes rat is from an inbred mutant colony of rats with spontaneous eosinophilia. In order to investigate the pathogenesis of the mes rat, the histopathology and hematology for 76 mes rats were examined at several weeks of age. Tissue eosinophilia developed at 8 weeks of age when the blood eosinophil was 500 cells per microliter or more. Subsequently, eosinophilia progressed with age, and splenic eosinophilopoiesis and erythropoiesis appeared simultaneously. Many inflammatory lesions were induced after 10 weeks of age when the blood eosinophils became 1,000 cells per microliter or more. Gastroenteritis and mesenteric lymphadenitis were seen in 44 of 47 (94%) and 31 of 47 (66%) rats, respectively, after 10 weeks of age. Aortitis that deteriorated with age was found in 19 of 39 (49%) rats after 12 weeks of age. Hepatic fibrosis was found in four rats that exhibited severe eosinophilia and anemia. These results are comparable to the features of a hypereosinophilic syndrome in humans and other animals.

Animals↗

PubMed2003

Pulmonary eosinophilia following lung transplantation for sarcoidosis in two patients.

Pulmonary eosinophilia is an uncommon problem in lung transplant recipients. We report the unique occurrence of two cases of pulmonary eosinophilia in pulmonary allografts for sarcoidosis. Both patients rapidly acquired bronchiolitis obliterans syndrome (BOS) after resolution of pulmonary eosinophilia. It is known that peripheral eosinophilia is a marker for pulmonary allograft rejection, but its potential in the pathogenesis of BOS is unclear.

Biopsy↗

PubMed1987

Pulmonary eosinophilia in coccidioidal infections.

Two cases of pulmonary eosinophilia associated with coccidioidal infections are reported. Pulmonary eosinophilia in these cases represents a hypersensitivity reaction to the fungus. Histologically, the pulmonary eosinophilia in these cases closely mimicked or appeared identical to idiopathic chronic eosinophilic pneumonia. Coccidioides immitis organisms were rare or absent in the areas of pulmonary eosinophilia. Recognition of this phenomenon is important for proper care of the patient.

Adolescent↗

PubMed1988

Eosinophilia, respiratory symptoms and pulmonary infiltrates in rubber workers.

This report describes a spectrum of respiratory illnesses associated with eosinophilia which occurred in a group of workers exposed to fumes from a synthetic rubber-based curing operation. Respiratory syndromes induced by this exposure included an acute sensitizing illness with dyspnea and wheezing in some workers and pulmonary infiltrates with eosinophilia in others. Another worker developed chronic obstruction of the airways with recurrent bronchitic illnesses. Mild to marked peripheral eosinophilia, up to 3,000/cu mm, was usually present in the symptomatic workers and in 11 of 30 asymptomatic workers. These cases illustrate the diversity of respiratory illnesses which may result from a common workplace exposure and reinforce the importance of considering occupational exposures in the differential diagnosis of peripheral eosinophilia.

Acute Disease↗

PubMed1989

Probability of malignancy in pleural fluid eosinophilia.

Pleural fluid eosinophilia is rare and is commonly considered as an indicator of good prognosis. In a series of 224 patients, pleural eosinophilia was present in four of 84 malignant cases; however, the incidence of malignancy in the presence of pleural eosinophilia was 0.40, being explained by a relatively high prevalence of malignancies in the population studied. Although pleural eosinophilia is rare in malignant effusions, it cannot be considered as indicating a good prognosis without taking into consideration the local prevalence of malignancies.

Eosinophilia↗

PubMed1984

Blood eosinophilia in bronchial asthma and its relationship to IgE-mediated reactions.

The correlation between blood eosinophilia and anti-IgE-mediated histamine release was investigated in 22 bronchial asthma patients with peripheral eosinophilia (over 8%). In the cases (Group A-1 and Group A-2) in which house dust was the specific antigen, significant histamine release from basophils was induced by anti-IgE and house dust. The result indicates a relationship between eosinophilia and the IgE-mediated mechanism of disease onset. In the cases (Group A-3) with RAST scores of 0+ and 1+ to house dust, the anti-IgE-induced histamine release varied from low to high percentages, and the participation of the IgE-mediated pathway was indicated in some cases. In the cases (Group B) with negative skin reactions, few patients had a family history of allergic disease. Their ages at onset were higher, and they demonstrated lower total IgE levels. These cases showed an extremely low percent of histamine release from basophils, which indicated the absence of a correlation between eosinophilia and IgE-mediated mechanisms.

Adolescent↗

PubMed1995

Microcirculatory segments identified with monoclonal antibody against alpha-smooth muscle actin: comparison between Kimura's disease and angiolymphoid hyperplasia with eosinophilia.

Microcirculatory systems, which can be divided into several segments, have crucial physiological functions. We investigated whether monoclonal antibody against alpha-smooth muscle actin (alpha SMA) was useful for the identification of microcirculatory segments, according to the structure of their periendothelial cells, in two pathological cutaneous conditions. We examined skin specimens from patients with Kimura's disease and with angiolymphoid hyperplasia with eosinophilia, since little information is available on microvascular segments in these conditions. Immunostaining for alpha SMA revealed the morphological characteristics of the periendothelial cells clearly enough to identify five segments in the proliferative microvessels of Kimura's disease and angiolymphoid hyperplasia with eosinophilia. In Kimura's disease, postcapillary venules were predominant, while each vascular segment in angiolymphoid hyperplasia with eosinophilia was uniform. Vessels without periendothelial cells were detected to a greater extent in angiolymphoid hyperplasia with eosinophilia than in Kimura's disease. The antibody against alpha SMA appeared to be useful in the observation of periendothelial cells for the identification of vascular segments in pathological cutaneous conditions.

Actins↗

PubMedDate not supplied

Patterns of nasal eosinophilia in allergy clinic patients as determined by swab and curette sampling.

The presence of eosinophils in nasal secretions often characterizes inflammatory disease in the nose and paranasal sinuses. This study analyzed differential associations between various clinical parameters and the presence of nasal eosinophilia in mucosal specimens obtained by two sampling methods (swab and curette-probe). Nasal mucosal secretions were obtained in patients attending an adult allergy clinic using both sampling methods for each patient. The presence of eosinophilia as determined by both methods had significant associations with 1) nasal mucosal pallor, 2) younger age, and 3) the presence of basophilic cells. To examine diagnostic characteristics of the two sampling methods of determining eosinophilia as a characteristic of allergic rhinitis, receiver operating characteristic (ROC) curves were evaluated for patients categorized as having allergic rhinitis on the basis of elevated aero-allergen specific IgE, and rhinitis based on either a) significant nasal mucosal appearance abnormalities, or b) a referring physician's diagnosis of rhinitis. The curette-probe determined nasal eosinophil quantitations had greater areas under the ROC curves when rhinitis was defined on the basis of mucosal appearance. On the other hand, the swab determined eosinophil quantitations had greater ROC curve areas when rhinitis was defined on the basis of referring diagnosis. In summary, nasal eosinophilia determined by curette or swab sampling has differences in strengths of their clinical associations.

Adult↗

PubMed1997

Eosinophilia associated with clonal T-cell proliferation.

Eosinophilia associated with the expansion of cloned T-cells is reviewed in relation to cytokine production. It has been proved that eosinophilopoiesis is caused by eosinophil-stimulating cytokines, including interleukin-5 (IL-5), granulocyte-macrophage colony-stimulating factor and interleukin-3, which are secreted from T-cells. Recently, we and other groups have reported several cases of eosinophilia including hypereosinophilic syndrome (HES) accompanied with proliferation of abnormal T-cells with an unusual phenotype CD3- CD4+ or CD3+ CD4- CD8- in the peripheral blood. The T-cells clonally proliferate, as confirmed by clonal rearrangements of the T-cell receptor (TCR) gene, and produce eosinophil-stimulating cytokines, especially IL-5, with or without stimulation in vitro. Although HES is defined by the combination of unexplained prolonged eosinophilia and evidence of organ involvement, these observations suggest that increased production of eosinophil-stimulating cytokines from the abnormal T-cells with phenotype CD3- CD4+ or CD3+ CD4- CD8- may cause eosinophilia, some of which have been diagnosed as HES.

CD3 Complex↗

PubMedDate not supplied

Simple pulmonary eosinophilia evaluated by means of FDG PET: the findings of 14 cases.

OBJECTIVE: We wanted to describe the findings of simple pulmonary eosinophilia with using 18 fluorodeoxyglucose (FDG) positron emission tomography (PET). MATERIALS AND METHODS: We analysed the findings of 14 patients who underwent thoracic computed tomography (CT) and PET, and then they were subsequently proven to have simple pulmonary eosinophilia. PET studies were performed in four patients with malignancy to evaluate for cancer metastasis, and PET scans were also done in 10 healthy subjects who underwent volunteer cancer screening. The PET scans were evaluated by using the maximum standardized uptake values (SUVs). The subjects' CT findings also were reviewed and correlated with the PET findings. RESULTS: A total of 42 nodules were detected on the CT scans. There were single nodules in three patients and multiple nodules in 11 patients (mean number of nodules: 3, range: 1-10, mean diameter: 9.5 mm+/-4.7). Twelve of 42 (28.6%) nodules showed FDG uptake and their mean maximum SUV was 2.5+/-1.6 (range: 0.6-5.3). Five of six solid nodules showed FDG uptake (2.2+/-1.1, range: 0.9-3.6), six of 11 semisolid nodules showed FDG uptake (3.1+/-1.8, range: 0.6-5.3) and one of 25 pure ground-glass opacity nodule showed a maximum SUV of 0.8. The maximum SUVs of seven nodules in five patients were greater than 2.5. The maximum SUVs were significantly different according to the nodule types (p < 0.001). CONCLUSION: Simple pulmonary eosinophilia commonly causes an increase in FDG uptake. Therefore, correlation of the PET findings with the CT findings or the peripheral eosinophil counts can help physicians arrive at the correct diagnosis of simple pulmonary eosinophilia.

Adult↗

PubMed1999

A practical workup for eosinophilia. You can investigate the most likely causes right in your office.

The vast majority of cases of eosinophilia in North America are caused by allergic processes. In individual cases, a short differential diagnosis of the most likely causes can be formulated on the basis of the absolute eosinophil count. The extensive laboratory workup previously recommended by some authorities is probably not justified unless detailed history taking and physical examination indicate a need for specific investigations. Although the possibility of missing an occult neoplasm has been used to justify extensive investigation, this is usually not necessary because most tumor-associated eosinophilia is accompanied by widely metastatic disease. History taking should emphasize the possibility of drug-induced or helminth-associated eosinophilia. If the history indicates travel, dietary, or other exposure risks, stool examination for ova and parasites is worthwhile. If a possible allergic cause is suspected, testing for evidence of atopy may be performed concomitantly with testing for parasitic infection. A follow-up white blood cell count with differential is recommended to ascertain whether eosinophilia has resolved. When an absolute eosinophil count of more than 1.5 x 10(9)/L persists for longer than 6 months, idiopathic hypereosinophilic syndrome must be ruled out.

Eosinophilia↗