Background and Methods. The importance of eosinophils in the pathogenesis of bronchial asthma is not established. In an attempt to evaluate the role of eosinophilic inflammation in asthma, we compared 10 normal subjects with 43 patients with chronic asthma, 19 of whom had severe disease as assessed by a clinical scoring method described by Aas and by pulmonary-function tests. Eosinophils were counted in peripheral blood and bronchoalveolar-lavage fluid, and in biopsy specimens obtained from the patients and post mortem from 8 subjects without asthma, but not from the 10 normal controls. Eosinophil cationic protein was titrated by radioimmunoassay in the bronchoalveolar-lavage fluid from all subjects and studied by immunohistochemistry in the biopsy specimens. Results. There was a significant increase in the number of peripheral-blood eosinophils in the patients that was correlated with the clinical severity of asthma (P<0.001) and pulmonary function (P<0.03). Levels of eosinophils and eosinophil ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199010113231505

Eosinophilic inflammation in asthma.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted diseases (STDs) were updated by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta on April 30-May 2, 2013. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2010 (MMWR Recomm Rep 2010;59 [No. RR-12]). These updated guidelines discuss 1) alternative treatment regimens for Neisseria gonorrhoeae; 2) the use of nucleic acid amplification tests for the diagnosis of trichomoniasis; 3) alternative treatment options for genital warts; 4) the role of Mycoplasma genitalium in urethritis/cervicitis and treatment-related implications; 5) updated HPV vaccine recommendations and counseling messages; 6) the management of persons who are transgender; 7) annual testing for hepatitis C in persons with HIV infection; 8) updated recommendations for diagnostic evaluation of urethritis; and 9) retesting to detect repeat infection. Physicians and other health-care providers can use these guidelines to assist in the prevention and treatment of STDs.

Sexually transmitted diseases treatment guidelines, 2015.

Introduction Acute Inflammation and Brief Symptoms Mechanisms: Experimentally Induced Allergic Reactions Clinical Consequences and Treatment Chronic Inflammation Site of the Inflammation in Asthma Cell Survival in Airway Tissues Characteristics of Chronic Inflammation Chronic Inflammation in the Different Forms of Asthma Clinic Consequences Treatment of Exacerbations Onset and Duration of Treatment Remodeling of the Airways Characteristics of Airways Remodeling in Asthma Clinical Consequences Radiographic Findings Treatment and Prevention of Airways Remodeling Conclusions

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.161.5.9903102

Asthma. From bronchoconstriction to airways inflammation and remodeling.

We measured bronchial reactivity to inhaled histamine and prepared electron micrographs from bronchial biopsies from 8 asthmatic patients who never smoked (2 females, 6 males, 18 to 62 yr of age). Judging from their clinical histories and the need for medication and long-term follow-up of PEF values, 2 of them had mild asthma, 3 moderately severe, and 3 severe asthma. They had not experienced respiratory infections for at least 2 months prior to the study. The result, obtained from the cumulative dose-response curve, was expressed as the provocative dose (PD20) of histamine producing a 20% fall in forced expiratory volume in one second (FEV1). In 5 patients, the PD20 varied from 0.049 mg to 2.234 mg. In the sixth patient, only PD15 could be measured (5.187 mg). In 2 patients, the low initial FEV1 values, because of severe, partly irreversible obstruction, prevented the measurement of bronchial reactivity. Bronchial biopsies were taken with rigid tube bronchoscopy from 3 levels: (1) at the carina of the right upper lobe, (2) at the opening of the right middle or lower lobe, and (3) inside the right lower lobe. The specimens were prepared for both light and electron microscopy. Fresh biopsies showed that asthma patients can have epithelial destruction at all levels of the airways. The ciliated cells appeared to be the most destroyed cell type in the epithelium. Intraepithelial nerves and mast cells were seen. Epithelial destruction in the respiratory tract of the asthma patients with mild to severe bronchial hyperresponsiveness was prominent enough to expose the epithelial nerves for specific or nonspecific stimuli.

Damage of the airway epithelium and bronchial reactivity in patients with asthma.

1. Damage of the Airway Epithelium and Bronchial : Reactivity in Patients with Asthma

Eosinophilia of lung and blood associated with injury to the mucociliary escalator and excessive shedding of bronchial epithelium are hallmarks of both allergic and nonallergic asthma. In vitro, the eosinophil granule major basic protein (MBP) is toxic to helminths and to mammalian cells, including human respiratory epithelium. The MBP-mediated damage to the respiratory epithelium consists of desquamation and frank destruction of ciliated cells. Increased sputum MBP concentration is a good marker for asthma, and patients treated for acute asthma have high levels of MBP in their sputa, which decrease after treatment. Peak sputum MBP levels approximate concentrations toxic to respiratory epithelium in vitro. In the lungs of patients who had died of asthma, MBP has been localized outside of the eosinophil in association with damage to the epithelium. Overall, these and other findings suggest the hypothesis that the eosinophil mediates damage to the respiratory epithelium and is the prime effector cell in the pathophysiology of asthma.

The eosinophil and the pathophysiology of asthma

Summary The eosinophil major basic protein (MBP) damages cells including those from organs whose dysfunction is associated with eosinophil infiltration. Concentrations of MBP in the toxic range were found in sputa from asthmatics, in pleural fluid and in sera. These findings suggest the hypothesis that the eosinophil produces damage to cells in disease.

Cytotoxic Properties of the Eosinophil Major Basic Protein

We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 µg/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 µg/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2-producing enzyme glucose oxidase (GO), Cl−, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3....

Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro.

Cytotoxic effects of the guinea pig eosinophil major basic protein on tracheal epithelium.

The eosinophil granule major basic protein (MBP) is toxic to parasites and mammalian cells. Because eosinophilia is characteristic of asthma, we tested the effect of MBP on bronchi and assayed sputa for this protein. We found that MBP damaged bronchial epithelium in vitro and produced changes that mimicked those in asthma. Radioimmunoassay of sputa from 100 consecutive patients with respiratory diseases revealed MBP levels above 0.1 mug/ml in 13 patients, and 11 of these had asthma. In 15 patient hospitalized for asthma, MBP levels of sputum were markedly elevated. Treatment with bronchodilators and glucocorticoids caused an increase peak expiratory flow rate, a reduction in blood eosinophils, and a decrease in the serum and sputum levels of MBP. The results indicate that eosinophil granule constituents are released into the bronchi in asthma and that measurement of sputum MBP may be useful in identifying asthma. The possibility that the eosinophil damages bronchial epithelium in asthma is discussed.

Evangelo Frigas

Papers

The eosinophil and the pathophysiology of asthma

Cytotoxic Properties of the Eosinophil Major Basic Protein

Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro.

Cytotoxic effects of the guinea pig eosinophil major basic protein on tracheal epithelium.

Elevated levels of the eosinophil granule major basic protein in the sputum of patients with bronchial asthma