ABSTRACT

I. Introduction 83

II. Do ECP Blood Serum Levels Correlate with Disease Activity and

Mucosal Hyperreactivity? 84

A. In Adult Patients with Allergic and Nonallergic Asthma

and COPD 84

Introduction 84

Patients with Allergic Asthma 84

Patients with Both Allergic and Nonallergic Asthma 85

Patients with COPD 86

B. In Children with Allergic and Nonallergic Asthma 87

Introduction 87

Investigations Showing No Correlations 87

Investigations Suggesting Correlations 88

Investigations Showing Statistically Significant Correlations 88

Explanations for a Lack of Correlation 89

C. In Adult Patients with Allergic Rhinitis 91

Introduction 91

Investigations Showing No Correlations 91

Investigations Showing Statistically Significant Correlations 92

D. In Children with Allergic Rhinitis 93

Introduction 93

Investigations Showing No Correlations 94

Investigations Showing Statistically Significant Correlations 94

III. Do ECP Levels in Local Body Fluids (Sputum,

Nasal Secretion) Correlate with Disease Activity

and Mucosal Hyperreactivity? 95

A. In Children and Adult Patients with Allergic and

Nonallergic Asthma and COPD 95

Introduction 95

Patients with Both Allergic and Nonallergic Asthma 95

Patients with COPD 97

Bronchoalveolar Challenge Tests 97

B. In Adult Patients with Allergic Rhinitis 97

Introduction 97

ECP Levels in Nasal Secretions After Allergen Challenge 98

ECP Levels in Nasal Secretions Under Natural Allergen

Exposure Within the Season 99

ECP Levels in Nasal Secretions in Different Forms of Rhinitis 100

ECP Levels in Nasal Secretions Under Therapy 100

C. In Children with Allergic Rhinitis 101

Introduction 101

ECP Levels in Nasal Secretions Under Natural Allergen

Exposure Within the Season 101

ECP Levels in Nasal Secretions Under Therapy 102

IV. Do ECP Blood Serum Levels Correlate with ECP Levels in Local

Body Fluids (Sputum, Nasal Secretion)? 102

A. Introduction 102

B. Correlation Between ECP Blood Serum Levels and ECP

Levels in Sputum or Bronchoalveolar Lavage Fluid 103

Introduction 103

Clinical Studies 103

Therapy Studies 103

Direct Control of the Correlation 104

C. Correlation Between ECP Blood Serum Levels and ECP

Levels in Nasal Secretions 104

Introduction 104

Investigations Showing No Correlation 104

Investigations Suggesting Correlations 105

V. Variation of ECP Levels 106

A. Variation of ECP Blood Serum Levels 106

Introduction 106

In Vivo 106

In Vitro 107

B. Variation of ECP Levels in Sputum and Bronchoalveolar

Lavage Fluid 108

In Vivo 108

In Vitro 108

C. Variation of ECP Levels in Nasal Secretion and Nasal

Lavage Fluid 108

In Vivo and In Vitro 108

Influence of Sampling Methods 109

VI. Summary 109

Acknowledgments 111

References 111

I. Introduction

Allergic rhinitis is a type I allergic reaction causing an inflammation of the nasal

mucosa. In type I allergies an immediate phase and a late phase of the allergic

reaction may occur. The immediate phase is caused by a mast cell degranulation

with the release of histamine and other mediators, whereas the late phase

is caused by an immigration of inflammatory cells into the mucosa. A cell type

with major importance among these inflammatory cells is the eosinophil cell

(1-4). During the late phase of the allergic reaction the eosinophil cells are

not only attracted but also activated, leading to a release of granular proteins,

which cause the mucosal inflammation. These granular proteins are major

basic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and eosino-

phil cationic protein (ECP) (5). Since the content of ECP in cells other than

eosinophil cells is negligible and since it is only released by activated eosinophil

cells (6), ECP is a good and specific indicator of eosinophil cell activity and turn-

over, and possibly of mucosal inflammation (7).