High Peripheral Eosinophil Count Research Articles

Obesity as a risk factor for increased asthma severity and allergic inflammation; cause or effect?

Obesity has been inconsistently shown to increase asthma morbidity, which may be partly explained by the fact that weight gain does not appear to affect all asthmatic subjects alike. Evidence to support this assertion comes from recent cluster studies showing that having a larger body mass index (BMI) is part of an asthma phenotype characterized by adult onset asthma, female preponderance and less atopy 1, 2. Also, a large epidemiological study showed stronger associations between asthma and obesity among non-allergic women 3. The fact that increasing BMI has been unexpectedly associated with reduced biomarkers of Th2-related inflammation, such as exhaled NO and sputum eosinophils also supports a relationship between obesity with predominantly non-Th2-mediated inflammation 4, 5. Although it is entirely expected that weight gain can worsen respiratory symptoms in most asthmatics, it is perhaps in this specific cluster that obesity is a major risk factor for increased asthma severity. Further, as shown by Dixon et al. the effects of weight loss on asthma differ according to the underlying clinical phenotype 6. In their study, obese asthmatics were prospectively evaluated at baseline and 1 year after bariatric surgery. Although all asthmatics experienced significant improvements in quality of life and asthma control, there was a significant interaction between weight loss and bronchial hyperresponsiveness, with the greatest improvements seen among those with normal IgE levels. As current evidence points towards the existence of predominantly non-Th2 obesity–asthma phenotype, the article by Fitzpatrick et al. 7 published on this issue of the journal, suggests that obesity is associated with increased asthma severity and allergic inflammation. This is a retrospective cross-sectional study comprised of a population of atopic, mostly African American asthmatic adults, of which 50% were obese. Compared with their leaner counterparts, obese asthmatics were more likely to be classified as having severe asthma and those with a BMI > 35 were more likely to use more inhaled and oral corticosteroids. Also, obesity was associated with increased serum IgE levels and increased blood neutrophils. Compared with leaner asthmatics, overweight, but not obese subjects, had higher peripheral eosinophil counts. How to then interpret these findings, which by showing an association between obesity and increased allergic inflammation, depart from what others have shown? Several characteristics related to the uniqueness of the study population and to the study design, may explain why Fitzpatrick et al. found these contrasting results. First, the presence of atopy determined by a history of skin allergy testing was an inclusion criterion that biased the study population towards greater indices of allergic inflammation. Second, among African Americans, elevated IgE levels are strongly associated with increased asthma severity 8, which via reduced physical activity and greater steroid use could lead to increase risk of obesity. Clearly, given the cross-sectional design of the study it is impossible to determine whether asthma severity preceded obesity. However, data from the Severe Asthma Research Program supports this assertion by showing that early onset asthmatics, which are also more likely to have atopy and greater allergic inflammation, increase their BMI at a steeper rate when compared with late-onset, less atopic asthmatics 9. There are important research and clinical implications that can be derived from this study. The generalizability of these results would imply that among atopic asthmatics of predominantly African Americans descent, obesity increases the odds for allergic inflammation; however, given our current understanding of asthma phenotypes, it is possible that in this case obesity is the result rather than the cause of increased asthma severity and elevated IgE levels. Although the authors argue that that obesity could lead to elevated IgE levels through an obesity-mediated pro-inflammatory state, an interaction between adiposity with asthma on biomarkers of inflammation has not been shown to occur in humans. Perhaps our inability to demonstrate this interaction results from heterogeneity of the susceptibility that asthmatics have to being obese. Just like not every asthmatic is sensitive to pollen, or cat dander; why should we expect obesity to be any different? In our quest to identify the mechanisms by which obesity affects asthma, perhaps we should, with equal enthusiasm, try to identify the cluster of asthmatics in whom disease process is more adversely affected by this condition (beyond increased dyspnoea); whether the adult onset asthmatic with less atopy constitute this phenotype, is yet to be proven. However, until we do this, it will be difficult to fully understand the underlying pathophysiological mechanisms and develop differential or personalized treatment approaches. Moreover, we will be unable to identify in cross-sectional studies, whether or not obesity is indeed a cause or an effect.

Nasal Symptoms and Sleep Problems in Chronic Rhinosinusitis

Objective: In recent years various studies have been conducted regarding the effects of CRS on the patient’s quality of life (QOL). There have, however, been few reports of its effects on the quality of sleep. Accordingly, we examined which factors are involved in sleep problems associated with CRS. Method: Multicenter prospective study. We analyzed 685 consecutive CRS patients between April 2007 and March 2008. All patients completed a QOL questionnaire and background parameters. The patients who had sleep problems (SP group) were compared with other patients in regard to nasal symptoms and background parameters. Results: A total of 148 patients (21.6%) had sleep problems. The scores for each of the nasal symptoms were significantly higher in the SP group. In addition, the sleep score was significantly higher in the patients with a complication of allergic rhinitis and the patients with high peripheral and tissue eosinophil counts. Logistic regression analysis found that nasal congestion, cough, and ear fullness were nasal symptoms that contributed to the SP group. Conclusion: This study indicated that, in addition to nasal symptoms, inflammatory conditions such as allergic rhinitis and eosinophilic inflammation have the potential to directly affect sleep problems. Logistic regression analysis revealed that subjective symptoms, such as nasal congestion, cough, etc, are closely related to sleep problems.

L’œsophagite à éosinophiles. Présentation, bilan allergologique et traitement : à propos de 22 cas

Eosinophilic esophagitis (EE) is a disorder characterized by severe eosinophilic infiltration of the esophagus, with dysphagia and gastroesophageal reflux disease (GERD) symptoms unresponsive to acid blockade therapy but responsive to the removal of dietary antigens. We report information relating to children diagnosed with EE in Nice, France, over a 6-year period. We conducted a retrospective study between January 1, 2004, and July 31, 2009, evaluating all children diagnosed with EE. Clinical and demographic data, endoscopic and histological findings, allergology data, and results of treatment were collected and evaluated. A total of 22 patients, 19 males, median age 9.5 years (range: 0.8-19 years) were reviewed: 7 presented isolated dysphagia, 6 presented GERD symptoms, and 9 both dysphagia and GERD symptoms. Endoscopically, 14 had multiple esophageal white plaques, 7 had linear furrowing, 5 had circular "tracheal" rings, and 5 esophageal narrowing. The median number of esophageal eosinophils/high power field (×400) was 30 (range: 15-80). Eosinophils were localized in the distal, middle, and upper esophagus. Immunoallergy analysis findings were: high peripheral eosinophil count (74%), high total IgE level (65%), high eosinophil cationic protein (ECP) level (90%) with a median value of 69.5 μg/l and high urinary leukotriene E4 (88%). Food antigen sensitization was positive in skin-prick testing in 11 of 18 and in atopy-patch testing in 9 of 17. Dietary restriction improved clinical symptoms in 5 of 10 and local corticotherapy with viscous budesonide improved clinical symptoms in 9 out of 10. EE diagnosis must be considered in children with dysphagia or GERD who do not respond to acid blockade therapy. ECP may be used to guide diagnosis. Local corticotherapy is effective.

Predictors and markers of resistance to neurotropic nematode infection in rodent host

Parasite-mediated selection is currently believed to play an important role in life-history evolution. To assess how simple hematoserological and biochemical condition indices reflect host immunocompetence and infection resistance controlled laboratory experiments are required. We addressed these issues by infecting laboratory rats with the standard dose of embryonated eggs of a neurotropic nematode Toxocara canis. Urine baseline corticosterone concentrations, measured 1 week before infection, predicted the number of nematode larvae later recovered from host brains. Thus, this noninvasive clinical marker appeared useful for assessment of potential infection resistance. Rats who had accumulated high number of larvae in their brains and muscle had large spleens and high peripheral eosinophil counts 17 days postinfection. This finding is consistent with the concept that induction of eosinophilic Th2 type humoral immune response benefits the parasite rather than host. Hence, excessive peripheral eosinophilia and spleen enlargement are not markers of efficient antiparasite response in larval toxocariasis.

Factors associated with recurrent hospitalizations in asthmatic children

Objective. – To determine preventable risk factors associated with recurrent hospitalization of children for acute asthma attacks. Methods. – A retrospective analysis of 288 asthmatic children between 6 and 15 years of age who were hospitalized between 31 December 1993 and 1 January 2000 was carried out. Results. – Admissions for asthma were higher in boys than in girls (male to female ratio 1.8). Of 288 children, 68 (23.6%) had multiple admissions, defined as a more than one admission per year during the follow-up period. The following factors were associated significantly with recurrent hospital admissions for asthma attacks: maternal smoking ( P < 0.02); frequent upper respiratory tract infection ( P < 0.001); high levels of total serum IgE ( P < 0.02); high peripheral blood eosinophil count ( P < 0.001); atopic dermatitis ( P < 0.001); and age less than 11 years ( P < 0.05). Using multivariate logistic regression analysis, among others factors only maternal smoking ( r = 0.24, P < 0.001) and frequent upper respiratory tract infection ( r = 0.37, P < 0.001) were significant factors for recurrent admissions. Conclusion. – Prevention of maternal smoking and frequent upper respiratory tract infections may be effective in decreasing re-admission to hospital in asthmatic children.

Drug-induced hepatocellular liver injury due to benzylpenicillin with evidence of lymphocyte sensitization

Background/Aims: Reports on drug-induced liver injury due to benzylpenicillin are scarce and predominantly describe cases of intrahepatic cholestasis. To our knowledge, no immunologically documented case of hepatocellular liver injury due to benzylpenicillin has been reported so far. Case Report: A previously healthy man required long-term therapy with benzylpenicillin because of vertebral spondylitis. After 4 weeks of treatment, liver tests showed a marked increase in transaminases associated with high peripheral eosinophil counts. Discontinuation of benzylpenicillin resulted in gradual recovery. Investigations: Levels of eosinophil cationic protein were elevated, indicating eosinophil activition and the presence of an immunoallergic reaction. Skin tests and assays for specific Ig E-antibodies to benzylpenicillin were negative, but lymphocyte transformation tests demonstrated T-cell sensitization to benzylpenicillin. Conclusion: According to current causality assessment schemes, our report constitutes a probable case of drug-induced hepatocellular liver injury due to benzylpenicillin.

Allergic colitis in infancy: clinical and pathologic aspects.

This study prospectively evaluated 35 consecutive infants who presented with fresh blood mixed with stools. The mean age at onset of bleeding was approximately 4 weeks. All infants were otherwise asymptomatic and exhibited normal growth and physical examinations. None had evidence of a bleeding diathesis, viral or bacterial enteritis, or necrotizing enterocolitis. Consent for limited colonoscopy and biopsy was obtained for 34 infants. Twenty-five had macroscopic colitis and 10 infants had marked nodular lymphoid hyperplasia. Thirty-one infants had histopathological evidence of colitis characterized by a marked eosinophilic infiltrate. Compared with 19 controls (age, 4.1 +/- 3.6 months) the mean number of eosinophils per high-power field was greater in the patients with colitis. Patients with colitis also had an elevated mean absolute peripheral eosinophil count and a low mean serum albumin compared to control values. The 31 infants with colitis were receiving solely breast milk (10), cow's milk formula (9), soya formula (9), breast milk with cow's milk formula (2), or nutramigen (1) at the time of presentation. Nineteen infants had rapid resolution of frank bleeding and gradual correction of serum albumin with dietary change. While limited colonoscopy and biopsy were useful in establishing a definitive diagnosis, a low serum albumin and high peripheral eosinophil count suggested the diagnosis. Colitis characterized histologically by > 20 eosinophils per high-power field is a common cause of rectal bleeding in otherwise healthy young infants. Resolution of bleeding and increase in serum albumin after dietary change suggest that this is an allergic colitis: however, the pathogenesis of this disorder needs further clarification.

Allergic Colitis in Infancy

SummaryThis study prospectively evaluated 35 consecutive infants who presented with fresh blood mixed with stools. The mean age at onset of bleeding was approximately 4 weeks. All infants were otherwise asymptomatic and exhibited normal growth and physical examinations. None had evidence of a bleeding diathesis, viral or bacterial enteritis, or necrotizing enterocolitis. Con sent for limited colonoscopy and biopsy was obtained for 34 infants. Twenty‐five had macroscopic colitis and 10 infants had marked nodular lymphoid hyperplasia. Thirty‐one infants had histopathological evidence of colitis characterized by a marked eosinophilic infiltrate. Compared with 19 controls (age, 4.1 ± 3.6 months) the mean number of eosinophils per high‐power field was greater in the patients with colitis. Patients with colitis also had an elevated mean absolute peripheral eosinophil count and a low mean serum albumin compared to control values.The 31 infants with colitis were receiving solely breast milk (10), cow's milk formula (9), soya formula (9), breast milk with cow's milk formula (2), or nutramigen (1) at the time of presentation. Nineteen infants had rapid resolution of frank bleeding and gradual correction of serum albumin with dietary change. While limited colonoscopy and biopsy were useful in establishing a definitive diagnosis, a low serum albumin and high peripheral eosinophil count suggested the diagnosis. Colitis characterized his‐tologically by &gt;20 eosinophils per high‐power field is a common cause of rectal bleeding in otherwise healthy young infants. Resolution of bleeding and increase in serum albumin after dietary change suggest that this is an allergic colitis: however, the pathogenesis of this disorder needs further clarification.

Utility of Fiberoptic Bronchoscopy in Nonresolving Pneumonia

Although fiberoptic bronchoscopy (FOB) has been traditionally used to evaluate nonresolving pneumonia, its efficacy is unknown. We, therefore, reviewed FOB in 35 consecutive patients who had (1) a roentgenographic infiltrate, (2) cough, (3) either temperature greater than 38.1 degrees C, leukocytosis, sputum production, (4) symptoms present for at least ten days, and antibiotic therapy for at least one week. Known lung cancer and AIDS were excluded. Fiberoptic bronchoscopy was diagnostic in 86 percent (12/14) in whom a specific cause was found. No patient had endobronchial cancer. Two patients with nondiagnostic FOB and persistent systemic symptoms had open lung biopsy specimens showing Wegener's granulomatosis and bronchiolitis obliterans with organizing pneumonia (BOOP). Twenty-one patients with nondiagnostic FOB had no final diagnoses other than community-acquired pneumonia. We conclude that FOB is extremely useful in finding a specific diagnosis for a nonresolving pneumonia when a specific diagnosis can be made. Fiberoptic bronchoscopy was most likely to yield a specific diagnosis in nonsmoking patients with multilobar infiltrates of long duration and could have been avoided in older, smoking, or otherwise compromised patients with lobar or segmental infiltrates with no decrease in diagnostic yield in our series.

L-Tryptophan Ingestion Associated with Eosinophilic Fasciitis but Not Progressive Systemic Sclerosis

To assess the use of L-tryptophan by patients with eosinophilic fasciitis and compare this with its use by patients with progressive systemic sclerosis (scleroderma). Retrospective and prospective analysis. Six patients with eosinophilic fasciitis were identified retrospectively and two prospectively. Retrospective identification of patients was done by questioning hospital-affiliated rheumatologists and dermatologists and by searching the hospital dermatopathology database. The patients with scleroderma or morphea were prospectively identified by questioning consecutive office patients with these established diagnoses. University of Pennsylvania rheumatology and dermatology practices. Eight patients with eosinophilic fasciitis; 40 consecutive patients with scleroderma (27 with diffuse cutaneous and 13, limited cutaneous disease); 3 patients with morphea. All eight patients with eosinophilic fasciitis had taken L-tryptophan before the onset of their disease. All had myalgias and high peripheral eosinophil counts (most greater than 5000 cells/mm3). Only 1 of 40 patients with scleroderma (no patients with morphea) had used L-tryptophan preceding illness (P less than 0.001 compared with eosinophilic fasciitis). Six patients with eosinophilic fasciitis had taken L-tryptophan for less than 8 months. One patient had taken it for 9 years before developing skin induration. Two patients were newly identified as having hypothyroidism; two developed neuropathy; and two had severe flexion contractures (several occurring in areas without skin induration). Five patients had low-titer antinuclear antibodies, indicating a possible autoimmune process. Most patients had only a partial response to systemic corticosteroid therapy. One patient has had important disease regression in response to isotretenoin therapy that was evident even while she continued to take L-tryptophan. L-Tryptophan use can lead to eosinophilic fasciitis whereas it does not appear to cause classic scleroderma. The disease process does not automatically remit after discontinuation of L-tryptophan-containing products.

In-vitro antibody-dependent killing of schistosomula of Schistosoma haematobium by human eosinophils.

Schistosomula of S. haematobium have been shown to be susceptible to in vitro killing by eosinophils in the presence of serum from an infected individual. The highest level of killing was found after 48 h in culture. Killing was related to the eosinophil to schistosomula ratio, being highest at 5000: 1. Killing was also related to serum concentration, being highest at a 1/10 final dilution, falling to background levels at a 1/120 final dilution. At a cell: target ratio of 2000: 1 and at a serum dilution of 1/10 eosinophils from subjects with high peripheral blood eosinophil counts were, cell for cell, more active in killing S. haematobium schistosomula than were eosinophils from subjects with lower counts. Sera taken from adults resident in an endemic area gave higher levels of killing in the presence of eosinophils than did sera taken from adults with no history of exposure.