Effects of treatment changes on asthma phenotype prevalence and airway neutrophil function.

Background: Asthma inflammatory phenotypes are often defined by relative cell counts of airway eosinophils/neutrophils. However, the importance of neutrophilia remains unclear, as does the effect of ICS treatment on asthma phenotypes and airway neutrophil function. The purpose of this study was to assess asthma phenotype prevalence/characteristics in a community setting, and, in a nested preliminary study, determine how treatment changes affect phenotype stability and inflammation, with particular focus on airway neutrophils.

Sputum basophils are increased in eosinophilic asthma compared with non-eosinophilic asthma phenotypes.

Sputum basophil numbers are increased in allergic asthmatics, but it is unclear what role airway basophils play in "TH2-low" asthma phenotypes. Using flow cytometry, we found that basophils were significantly increased in all asthmatics (n=26) compared with healthy controls (n=8) (P=0.007) with highest levels observed in eosinophilic asthma (EA); median 0.

Absence of airway inflammation in a large proportion of adolescents with asthma.

Background And Objective: Neutrophilic inflammation has been implicated in non-eosinophilic asthma (NEA) in adults, but little is known about NEA in children/adolescents. We assessed clinical and inflammatory characteristics of NEA in adolescent asthma.

Methods: Airway inflammation, sputum endotoxin, airway hyper-reactivity, atopy and lung function were assessed in 77 adolescents with asthma and 68 without asthma (12-17 years).

Relationship between airway neutrophilia and ageing in asthmatics and non-asthmatics.

Background And Objective: Increased sputum neutrophilia has been observed in asthma, but also during normal ageing in asthmatics and non-asthmatics. It remains unclear what constitutes 'normal' neutrophil levels in different age groups.

Methods: We assessed the relationship between age and airway neutrophils of 194 asthmatics and 243 non-asthmatics (age range: 6-80 years).

Identifying leukocyte populations in fresh and cryopreserved sputum using flow cytometry.

Background: Airway inflammation is commonly assessed by sputum induction followed by a differential cell count (DCC) using light microscopy. This method is prone to intercounter variability and poor reproducibility. We aimed to develop a more objective method using flow cytometry (FCM).

Importance of allergy in asthma: an epidemiologic perspective.

There has been a global epidemic of asthma during the past half-century. More recently, the prevalence has leveled off or declined in many Western countries, whereas the prevalence in less affluent nations is still increasing. The reasons for this and the different geographical patterns of asthma prevalence remain unclear.

Measurement of exhaled nitric oxide in a general population sample: a comparison of the Medisoft HypAir FE(NO) and Aerocrine NIOX analyzers.

Background And Objective: Measuring the fraction of nitric oxide in exhaled breath (FE(NO)) is increasingly utilized to assess airway inflammation in asthma. The primary aim of this study was to compare exhaled nitric oxide measurements obtained using two devices from different manufacturers, that is, the recently marketed portable and electrochemical-based Medisoft HypAir FE(NO) and the well-established chemiluminescence-based Aerocrine NIOX analyzer, in an unselected population.

Methods: FE(NO) measurements were conducted in 106 subjects (86 healthy; 20 asthmatic; 56.

Bromotyrosines in sputum proteins and treatment effects of terbutaline and budesonide in asthma.

Background: Inhaled corticosteroids are widely used in the treatment of persistent asthma, usually combined with inhaled beta2-agonists. Previous research suggests that short-acting beta2-agonists (SABAs) may downregulate the anti-inflammatory effects of inhaled corticosteroids, thereby increasing asthma morbidity.

Objective: To determine whether 3-bromotyrosine and 3,5-dibromotyrosine levels, specific markers of eosinophil activation, reflect treatment effects on airway inflammation of inhaled corticosteroids and SABAs and support previous conclusions.

Suitability of forced expiratory volume in 1 second/forced vital capacity vs percentage of predicted forced expiratory volume in 1 second for the classification of asthma severity in adolescents.

Objective: To determine whether lung function alters asthma severity based on symptom history in asthmatic adolescents.

Design: Data on asthma symptoms and lung function were collected from adolescents randomly selected from the general population.

Setting: Five schools from the central Wellington, New Zealand, area during 2003 to 2005.

Asthma control in a random sample of New Zealand adolescent asthmatics.

Asthma control, defined by asthma symptoms and lung function, and asthma medication use, was assessed in 123 adolescent asthmatics. Sputum eosinophilia (>or= 2.5% eosinophils) and bronchial hyperresponsiveness (BHR) to hypertonic saline were also measured to assess whether these additional objective parameters might aid in determining asthma control; 54.

Mechanism of nitrite oxidation by eosinophil peroxidase: implications for oxidant production and nitration by eosinophils.

Eosinophil peroxidase is a haem enzyme of eosinophils that is implicated in oxidative tissue injury in asthma. It uses hydrogen peroxide to oxidize thiocyanate and bromide to their respective hypohalous acids. Nitrite is also a substrate for eosinophil peroxidase.

Eosinophil peroxidase produces hypobromous acid in the airways of stable asthmatics.

Eosinophil peroxidase and myeloperoxidase use hydrogen peroxide to produce hypobromous acid and hypochlorous acid. These powerful oxidants may damage the lungs if they are produced as part of the inflammatory response in asthma. The aim of this study was to determine if peroxidases generate hypohalous acids in the airways of individuals with stable asthma, and if they affect lung function.

Substrates and products of eosinophil peroxidase.

Eosinophil peroxidase has been implicated in promoting oxidative tissue damage in a variety of inflammatory conditions, including asthma. It uses H(2)O(2) to oxidize chloride, bromide and thiocyanate to their respective hypohalous acids. The aim of this study was to establish which oxidants eosinophil peroxidase produces under physiological conditions.

Nitrite as a substrate and inhibitor of myeloperoxidase. Implications for nitration and hypochlorous acid production at sites of inflammation.

Myeloperoxidase is a heme enzyme of neutrophils that uses hydrogen peroxide to oxidize chloride to hypochlorous acid. Recently, it has been shown to catalyze nitration of tyrosine. In this study we have investigated the mechanism by which it oxidizes nitrite and promotes nitration of tyrosyl residues.

Thiocyanate and chloride as competing substrates for myeloperoxidase.

The neutrophil enzyme myeloperoxidase uses H2O2 to oxidize chloride, bromide, iodide and thiocyanate to their respective hypohalous acids. Chloride is considered to be the physiological substrate. However, a detailed kinetic study of its substrate preference has not been undertaken.

Molecular characterization of antigenic polymorphisms (Ond(a) and Mart(a)) of the beta 2 family recognized by human leukocyte alloantisera.

We show that the previously described alloantisera Ond and Mart, which recognize the alloantigens Ond(a) and Mart(a), react with polymorphic variants of alpha L and alpha M subunits of the beta 2 integrin family (CD11a and CD11b molecules). This was shown by testing the alloantisera in a monoclonal antibody-specific immobilization of leukocyte antigens, immunoprecipitation, and immunofluorescence assay against cells from normal donors and from patients with leukocyte adhesion deficiency (beta 2 intergrin deficient). To elucidate the molecular basis of the Ond(a) and Mart(a) alloantigens, RNA was isolated from mononuclear leukocytes derived from individuals of known serologic phenotype.

Further characterization of the NB 1 antigen as a variably expressed 56-62 kD GPI-linked glycoprotein of plasma membranes and specific granules of neutrophils.

The human neutrophil-specific alloantigen NB1 was identified as a glycosyl-phosphatidylinositol (GPI)-anchored N-glycosylated protein of M(r) 56-62 kD under reducing conditions. Under non-reducing conditions its M(r) was 49-55 kD. This glycoprotein antigen was found to be expressed by only a subpopulation of normal donor neutrophils, and could not be detected on other blood cells.

Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count.

Objective: To determine the efficacy of antenatal low dose oral betamethasone in preventing neonatal thrombocytopenia and/or bleeding in infants of mothers with idiopathic thrombocytopenic purpura (ITP).

Setting: Hospital department of obstetrics and gynaecology, referral centre.

Patients: 41 pregnancies in 38 women were randomized.

Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10.

The antigen recognized by the monoclonal antibody Ki-67 is a proliferation-related nucleolus-associated constituent used as a marker for cycling cells in tumor diagnosis. Antibody Ki-67 reacts with human proliferating cells, but not with hamster and mouse cells. Expression of the Ki-67 antigen was studied in a panel of human-rodent somatic cell hybrids.

Autoimmunity against blood cells in human immunodeficiency-virus (HIV) infection.

In persons with AIDS or at risk from AIDS, autoantibodies against platelets and granulocytes were frequently detected. Platelet-bound immunoglobulins were demonstrated by immunofluorescence in all 16 patients with AIDS, in five out of seven patients with AIDS-related complex/persistent generalized lymphadenopathy (ARC/PGL) and even in seven of 10 healthy sexually active homosexual men. Granulocyte-bound immunoglobulins were found by immunofluorescence in 12 of the 16 AIDS patients, five of the seven patients with ARC/PGL and two of the 10 symptomless men.

Clinical significance of positive platelet immunofluorescence test in thrombocytopenia.

The sensitivity and specificity of the platelet immunofluorescence test for the diagnosis of idiopathic thrombocytopenia (ITP) was studied in a series of 255 patients. Patients' platelets were tested directly. Diethyl-ether eluates of these platelets and patients' sera were tested indirectly with normal donor platelets.

Alloimmunization against the platelet-specific Zwa antigen, resulting in neonatal alloimmune thrombocytopenia or posttransfusion purpura, is associated with the supertypic DRw52 antigen including DR3 and DRw6.

The strong association between HLA-DR3 and Zwa alloimmunization in Zwa-negative mothers, resulting in the production of anti-Zwa antibodies and ultimately in neonatal alloimmune thrombocytopenic purpura (NAITP) in the newborn, could be confirmed. In addition, we have shown an equally strong association between HLA-DR3 and Zwa alloimmunization in Zwa-negative recipients of blood transfusions, resulting in posttransfusion purpura (PTP). However, the strongest association both in mothers of NAITP patients and in PTP patients was observed with the supertypic DRw52 antigen.