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Serum eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in childhood asthma: the influence of atopy.

The purpose of this study was to determine the value of serum measurements of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in diagnosing asthma in children, and to investigate the influence of concomitant allergic diseases and atopic sensitization, assessed by skin prick tests (SPT), on these markers. ECP and EPX were determined in 36 children with asthma, in 33 children with other symptoms from lower airways disease (OSLA), and in 166 control children. Sixteen children with asthma but no anti-inflammatory therapy had significantly higher concentrations of ECP and EPX (ECP: 27.5 microg/L, P < 0.001; EPX: 59.9 microg/L, P < 0.001) than the control children (ECP: 11.2 microg/L; EPX: 26.2 microg/L). In the 20 children on anti-inflammatory therapy, ECP values were similar to those of controls. The children with OSLA (ECP: 13.6 microg/L, P < 0.01; EPX: 47.2 microg/L, P < 0.001) differed significantly from controls. When using the value of 24.7 microg/L (97.5 percentile in the 68 non-atopic controls) as a pathologic upper limit for ECP, 10 (63%) of the 16 asthmatic children on no maintenance medication, two (10%) of the 20 asthmatics on maintenance therapy, and 11 (33%) of the 33 children with OSLA had high ECP; the same figure was only 18 (11%) in the 166 control children. Both ECP and EPX had a significant association with allergic disorders and with SPT reactivity. In multivariate logistic regression analysis, an elevated ECP was significantly associated with asthma (OR 2.3, 95%CI 1.1-4.9) and atopic dermatitis (2.9, 1.2-6.9), and an elevated EPX was significantly associated with asthma (2.61, 1.19-5.74) and allergic rhinoconjunctivitis (5.23, 1.46-18.73). We conclude that serum concentrations of both ECP and EPX are higher in asthmatic than in healthy children. However, other allergic diseases, such as allergic rhinoconjunctivitis, atopic dermatitis, and allergic skin sensitization also raise the concentrations of these markers. This limits their usefulness in the diagnosis of childhood asthma.

Anti-Inflammatory Agents↗

Eosinophil cationic protein and eosinophil protein X: human amniotic fluid concentrations and gestational tissue content at term.

The aim of this study was to determine the presence and concentration of immunoreactive eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in human amniotic fluid at term and assess labour-associated changes in their mean concentrations. In addition, ECP and EPX content in term amnion, choriodecidua and placenta obtained before and after labour and delivery was established. Immunoreactive ECP and EPX were identified in all samples of amniotic fluid (n=47) and gestational tissue (n=60) assayed. EPX was quantitatively more abundant than ECP in both amniotic fluid and gestational tissues. In amniotic fluid, ECP and EPX concentrations increased 8-fold (P<0.02) and 1.5-fold (P<0.02), respectively, with labour onset. In gestational tissues, a labour-associated change in tissue content was only identified for ECP in choriodecidua, which increased 1.9-fold with labour and delivery (P<0.01). The labour-associated increase in amniotic fluid concentrations of ECP and EPX demonstrated in this study is consistent with the well-characterized role of these proteins in inflammatory reactions. It remains to be established whether the observed increase in ECP and EPX amniotic fluid concentrations is an epiphenomenon of labour onset or is involved causally in this process.

Adult↗

Lack of relationship between eosinophil cationic protein and eosinophil protein X in nasal lavage and urine and the severity of childhood asthma in a 6-month follow-up study.

BACKGROUND: Recent studies suggest that eosinophil cationic protein (ECP) and eosinophil protein X (EPX) may be valuable markers of airway inflammation in various body fluids of asthmatic children. Most of these studies have relied on a single measure of inflammatory markers. OBJECTIVE: We measured ECP and EPX in nasal lavage fluids (NALF) and urine samples in children with asthma over a 6-month period to study the relationship between inflammatory markers and clinical severity. METHODS: Fourteen children with mild persisting asthma (mean age 11.7 years, SD 2.2) were recruited. All patients were on therapy including inhaled steroids. For a 6-month period asthma severity was monitored by at least monthly physical examination and pulmonary function tests. Daily morning and evening PEF, asthma symptoms and medication were recorded in diaries for the whole study period. Telephone interviews were performed between visits and additional visits were done in case of an increase in asthmatic symptoms or drop of PEF values under 80% of best value. An exacerbation was defined by a fall of FEV1 > 10% and an increase in asthma symptoms and additional need of beta2-agonist. NALF and urine samples were obtained at each visit and analysed for ECP (NALF only) and EPX. RESULTS: Mean observation time was 186.4 days (SD 19.8). Thirteen patients completed the study. During the study period 11 exacerbations were observed in six patients. No significant associations between PEF, PEF variability (amplitude % of mean), daily symptoms, additional beta2-agonist, FEV1 and MEF50 and nasal ECP, nasal EPX and urinary EPX were found. However, at exacerbations an average increase of nasal ECP (9.3 vs 50.3 microg/L) and EPX (nasal EPX 36.4 vs 141.7 microg/L, urinary EPX 46.4 vs 74.1 microg/mmol creatinine) was observed. CONCLUSION: Serial measurements of ECP and EPX in NALF and urine samples do not provide additional information for the practical management in monitoring childhood asthma.

Adolescent↗

Eosinophil protein X and eosinophil cationic protein as indicators of intestinal inflammation in infants with atopic eczema and food allergy.

BACKGROUND: The aim of this study was to evaluate the presence of allergic intestinal inflammation in infants with food allergy and atopic eczema before and after elimination diet, and to evaluate the use of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) in the monitoring of inflammatory activity. METHODS: The study material comprised 25 infants with atopic dermatitis and food allergy. Thirteen healthy infants served as controls. Faecal and serum samples were collected before an elimination diet (on the first visit to the hospital) and approximately 3 months later for the determination of EPX and ECP. RESULTS: Before the elimination diet, infants with atopic dermatitis demonstrated markedly higher faecal concentrations of EPX and ECP than healthy controls (P = 0. 0003, P < 0.0001, respectively). The faecal concentrations of EPX and ECP showed a distinct decrease as a result of an adequate elimination diet in patients with favourable clinical response (P = 0.0027, P = 0.004, respectively). CONCLUSIONS: The results indicate the presence of marked intestinal inflammation in patients with atopic dermatitis and food allergy. The determination of faecal ECP and especially of faecal EPX provides a promising noninvasive tool in monitoring intestinal inflammation and disease activity in infants with atopic eczema and food allergy.

Biomarkers↗

Eosinophils, but not eosinophil peroxidase or major basic protein, are important for host protection in experimental Brugia pahangi infection.

The attenuation of eosinophilia by the administration of monoclonal antibodies to CCR3 consistently correlates with impairment in worm elimination following primary intraperitoneal Brugia pahangi infections in mice. Host protection was unimpaired in mice deficient in eosinophil peroxidase (EPO) or major basic protein 1 (MBP-1), suggesting that eosinophils are essential in host protection but that neither EPO nor MBP-1 alone is.

Animals↗

Eosinophilic papulocrustous dermatitis (miliary dermatitis) and eosinophilic inflammatory bowel disease in two cats.

Two cats with chronic eosinophilic skin disease were investigated. The clinical investigation of the skin disease in one cat was limited and inflammatory bowel disease was diagnosed post mortem. A history of weight loss and a palpably thickened bowel in the second cat suggested concurrent gastrointestinal disease. Diagnosis of inflammatory bowel disease was confirmed on biopsy. Treatment with azathioprine and methylprednisolone acetate resolved the signs of gastrointestinal disease, the pruritus and 95% of the skin lesions. The concurrence of eosinophilic papulocrustous dermatitis and eosinophilic bowel disease raises the possibility of their being linked bv a common aetiology or pathophysiology.

Journal Article↗

Massive eosinophilic ascites: differential diagnosis between idiopathic hypereosinophilic syndrome and eosinophilic gastroenteritis.

This paper describes a patient with massive eosinophilic ascites as presenting manifestation probably due to idiopathic hypereosinophilic syndrome. Eosinophilic ascites and stomach wall involvement were the first detected abnormalities. The subsequent course was characterised by interstitial pulmonary disease and pleural and pericardial effusion. Grand mal epilepsy and numbness of the left arm indicated central nervous system involvement. Treatment with corticosteroids resulted in complete remission. The differential diagnosis of eosinophilic gastroenteritis and idiopathic hypereosinophilic syndrome is discussed.

Aged↗

Chronic bronchiolitis with associated eosinophilic lung disease (eosinophilic bronchiolitis).

We encountered an adult patient with dyspnea, eosinophilia and bronchiolitis. He was diagnosed as having diffuse panbronchiolitis, and was treated with erythromycin for 3 years, but his symptoms had gradually worsened. Bronchoalveolar lavage showed marked eosinophilia, and video-assisted thoracoscopic lung biopsy revealed chronic bronchiolitis with associated eosinophilic lung disease (eosinophilic bronchiolitis). To our knowledge, no case of eosinophilic bronchiolitis has been reported in the literature.

Bronchiolitis↗

Comparison of the pathology of fascia in eosinophilic myalgia syndrome patients and idiopathic eosinophilic fasciitis.

The L-tryptophan eosinophilic myalgia syndrome (EMS) clinically has some similarities with idiopathic eosinophilic fasciitis (EF). In order to study the pathology of both syndromes, we analyzed 21 biopsies of patients with EMS and 8 with idiopathic EF. In both diseases there is dermal and fascial mucin and dermal edema, but this was more common in EMS. EMS is also characterized by dilated lymphatics, dermal and septal sclerosis and macrophage-rich inflammation. Neural inflammation was seen in 4 of the cases with EMS and in none with idiopathic EF. In both syndromes, there are many histopathological similarities. The differences may be due to sampling and to sample size. The nerve lesions of EMS may result from the nature of lymphocyte-macrophage inflammation, or the effect of the eosinophil neurotoxin and may not be a primary event.

Biopsy↗

Visceral larva migrans due to Ascaris suum which presented with eosinophilic pneumonia and multiple intra-hepatic lesions with severe eosinophil infiltration--outbreak in a Japanese area other than Kyushu.

A 32-year-old man presented with the chief complaint of severe cough. Examination of peripheral blood showed a marked increase in eosinophils. Chest CT demonstrated multiple ground glass opacities in both lungs. Bronchoalveolar lavage showed abundant eosinophils. Abdominal CT demonstrated multiple low attenuation areas in the liver. Liver biopsy with ultrasonography revealed severe eosinophil infiltrations around the portal veins. Serologically, a multi-dot enzyme linked immunosorbent assay (DOT-ELISA) and ELISA inhibition test using microtiter plates were positive for Ascaris suum. Thus, visceral larva migrans due to Ascaris suum was diagnosed. Outbreaks of this disease in Japan have previously been confined to the Kyushu area. The present case which occurred outside that area, illustrates the importance of constant attention to the epidemiology of this disease.

Adult↗

[A case of minocycline-induced eosinophilic pneumonia presenting with multiple white eosinophilic plaques in the tracheobronchial mucosa].

A 45-year-old man was admitted with a severe dry cough and fever. He had been given 100 mg/day of minocycline and other drugs for 9 days to treat hematopyuria. Chest X-ray film showed multiple nodular shadows with diffuse reticular shadows. After all the drugs were discontinued, the fever and the shadows improved, but the severe dry cough persisted. The day 4 bronchofiberscopic findings included multiple white plaques in the tracheobronchial mucosa. Punch biopsy specimens obtained from the white plaques revealed severe eosinophil infiltration, and the eosinophil count in the bronchoalveolar lavage fluid had increased (differential count 23%). After three days of 125 mg/day of methylprednisolone sodium succinate injection therapy, the severe cough, the X-ray shadows and the white plaques disappeared. With a positive result in the lymphocyte migration inhibition test, the patient's condition was diagnosed as minocycline-induced eosinophilic pneumonia.

Anti-Bacterial Agents↗

[Eosinophilic-like erythema: a clinical subset of Wells' eosinophilic cellulitis responding to antimalarial drugs?].

BACKGROUND: Limits of Wells'syndrome, a nosologically enlarged entity defined after classic eosinophilic cellulitis, are imprecise. We report on a new "frontier" case, remarkable in its clinical pattern and its high sensitivity to antimalarial drugs. CASE REPORT: A 35-year-old woman was referred for evaluation of recurrent inflammatory, figurated and often annular lesions, mainly located on the trunk and the proximal parts of the limbs, associated with significant peripheral eosinophilia and featuring dense perivascular infiltrates throughout the dermis with abundant eosinophils but without any "flame figure". These lesions responded dramatically to protracted treatment with hydroxychloroquine. DISCUSSION: The relationship of this affection to Wells' syndrome is discussed along with its possible similarities to the sparse reports of so-called eosinophilic annular erythema.

Adult↗

[Chronic eosinophilic pulmonitis with eosinophilic pleurisy. A report on 2 clinical cases seen by the authors].

We discuss the cases of two patients affected with chronic eosinophilic pneumonia (CEP) pleurisy and eosinophilia in pleural effusion, not previously mentioned in the literature, to point out their peculiarity, to consider differential diagnosis and the effect of steroid therapy. Both patients, a 57-year-old man and a 55-year-old woman, were atopic: they had been suffering from allergic rhinitis and asthma for several years when they suffered sudden onset of cough, dyspnea and thoracic pain. This symptomatology persisted for more than 6 weeks. Chest radiography highlighted pulmonary infiltrates, not fixed in the first case, fixed in the second. The laboratory features revealed eosinophilia in peripheral blood and in pleural effusion. These data conformed to the criteria suggested by Jederlinic et al. for the diagnosis of chronic eosinophilic pneumonia. Tuberculosis had been present in the remote history of the second case; the repeated research for mycobacteria was negative, and no improvement was seen after antitubercular chemotherapy for one month. We excluded the diagnosis of allergic bronchopulmonary aspergillosis because of the absence of both precipitating antibodies against Aspergillus fumigatus and bronchiectasis. Neither vasculitis nor autoantibodies were found; possible drug-related correlations were excluded; culture data and serological researches for infections were negative in both cases; no involvement of other districts correlated to hypereosinophilia was evidenced. Clinical and radiological remission was obtained in both cases after steroid therapy for a month at the dosage of 1-2 mg/kg daily. No clinical recurrence was seen during a follow-up period of 6 months. Pleural effusion has already been reported in patients with CEP, while we have not found any references to pleural fluid eosinophilia in this disease; this finding has instead been already reported in patients affected with acute eosinophilic pneumonia or hypereosinophilic syndrome.

Chronic Disease↗

Isolated eosinophilic coronary arteritis and eosinophilic myocarditis. A limited form of Churg-Strauss syndrome.

Eosinophilic coronary arteritis is rare, and it occurs principally as a manifestation of cardiac involvement in Churg-Strauss syndrome (allergic granulomatosis and angiitis). A 39-year-old white man, who was an asthmatic, died suddenly and unexpectedly. Autopsy showed isolated eosinophilic coronary arteritis associated with myocardial necrosis, and isolated eosinophilic myocarditis as the cause of death. This limited form of Churg-Strauss syndrome, to our knowledge, has not been reported previously.

Adult↗

Eosinophilic enteritis associated with chronic eosinophilic pneumonia.

A case of eosinophilic pneumonia and eosinophilic infiltration of the small bowel and colon is reported. The patient presented with nonspecific chest and abdominal symptoms, and lack of response to therapy for presumed pneumonia. Further investigation including lung, muscle, and gastrointestinal tract biopsies revealed eosinophilic infiltration of the lung and gastrointestinal tract, an association that does not appear to have been previously documented.

Adult↗

The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure.

Two groups of birch pollen--allergic patients with seasonal rhinoconjunctivitis and asthma were followed during two consecutive birch-pollen seasons, one group, N = 10, during a season with high pollen load, and one group, N = 15, during a season of low pollen load. Half the patients were treated with immunotherapy (IT) for 3 and 4 years, respectively. The other half of the patients served as control group (non-IT). Bronchoalveolar lavage (BAL) was performed once before each season and once during the pollen season. Eosinophil (EOS) numbers in BAL were increased (p less than 0.01) during the season with high pollen load but not in the season with a low pollen load, and this increment was absent in the IT-treated group. Also, the EOS cationic protein levels were raised in the non-IT-treated group during the season with a high pollen load. The levels of EOS and neutrophil chemotactic activity were raised in BAL in both seasons in the non-IT-treated group compared with the IT-treated group (p less than 0.02, p less than 0.003, p less than 0.04, and p less than 0.005 in high- and low-load pollen season, respectively). Serum and BAL eosinophil chemotactic activity (ECA) were positively correlated (p less than 0.001). We conclude that there is an influx of active EOSs into the lung of pollen-allergic patients with asthma during a pollen season, which may be abrogated by IT. Furthermore, the generation of ECA appears to be an extremely sensitive marker of antigenic exposure, and the potent inhibition of the generation of ECA by IT may provide a clue as to the mechanism of this treatment.

Adolescent↗

Expressions of the VLA-4, LFA-1 and Mac-1 integrins in eosinophil migration in a case of chronic eosinophilic leukaemia.

Migration of eosinophil (Eo) into tissues is a hallmark of chronic eosinophilic leukaemia (CEL), but the exact mechanism involved in cell migration is unknown. We report on a patient with CEL who presented high expressions of VLA-4, LFA-1 and Mac-1 integrins on the Eo surface, increased chemotaxis of Eo to eotaxin, decreased chemotaxis of Eo after inhibition of the cyclic guanosine monophosphate (cGMP), and a high level of intracellular cGMP. These findings suggest that an upregulation of expression of these integrins on Eo surface and a high intracellular level of cGMP may be involved in the increased Eo migration observed in our CEL patient. However, the definitive roles of these molecules in the proliferation and migration of Eo in CEL disease require wider confirmation by analysis of additional patients with the disease.

Cell Movement↗

Circadian variations in serum eosinophil cationic protein, and serum and urine eosinophil protein X.

Biochemical evaluation of inflammation may be a useful adjunct to measures of pulmonary function and symptoms in children with asthma. However, little data have been provided to validate the markers in children. The aim of the present study was to assess circadian variations in serum eosinophil cationic protein (ECP), and serum and urine eosinophil protein X (EPX) in children. Five girls and two boys aged 10-14 years were studied. The first sample of urine consisted of urine collected from 24.00 hours the night before until 08.00 hours on the morning of the day of investigation. Thereafter urine was collected at 4-h intervals until 24.00 hours and in another 8-h interval from 24.00 to 08.00 hours. Blood samples for assessment of serum ECP and serum EPX were collected every 2 h during the 24 h. Statistically significant circadian variations in serum ECP (F=3.2, p=0.002), serum EPX (F=3.1, p=0.002) and in urine EPX/creatinine (F=5.4, p=0.003) were detected. The concentrations were higher during the night compared to daytime. Peak levels of serum ECP (mean [+/- SEM]) were found at 06.00 hours (16.3 [5.3] micro g/l), trough levels at 08.00 hours (3.9 [0.7] micro g/l) (p=0.01). Peak levels of serum EPX were seen at 06.00 (43.7 [9.5] micro g/l) with trough levels at 12.00 hours (22.0 [3.5] micro g/l) (p=0.01). Peak levels of urine EPX/creatinine occurred in urine collected from 24.00 to 08.00 hours (90.0 [27.7] micro g/mmol), trough levels in the 16.00-20.00 hours sample (29.7 [8.9] micro g/mmol) (p=0.02). Serum ECP, serum EPX and urine EPX exhibit a circadian variation in children with nocturnal and early morning peak levels. To avoid confounding influence from circadian variations in ECP and EPX in clinical studies blood or urine should be sampled at consistent times.

Adolescent↗