Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.

Background: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways.

Leukotriene receptors are differently expressed in fibroblast from peripheral versus central airways in asthmatics and healthy controls.

Leukotrienes are involved in airway inflammation, and are believed to stimulate airway remodeling in asthma. The aim of the project was to investigate the expression of leukotriene receptors in peripheral and central airway fibroblasts. Peripheral and central airway fibroblasts, from asthmatics and healthy controls, were investigated for the amount of cysteinyl-leukotriene receptors (CysLT(1) and CysLT(2)), leukotriene B(4) receptors (BLT(1) and BLT(2)), IL-13 receptor-α(1) (IL-13Rα(1)) and the IL-4 receptor (IL-4R).

TGFβ-induced matrix production by bronchial fibroblasts in asthma: budesonide and formoterol effects.

To investigate the mechanisms of enhanced airway deposition of subepithelial collagen in asthma and its sensitivity to drug therapy with combination of an inhaled glucocorticosteroid (GC) and a long-acting β(2)-agonist (LABA), a cell model system involving bronchial fibroblasts derived from biopsies from patients with stable mild-to-moderate asthma has been used. To mimic unstable conditions and severe asthma, fibroblasts were stimulated ex vivo with TGFβ1. Primary fibroblasts established from central bronchial biopsies from 8 asthmatic patients were incubated for 24 h with 0.

Targeting small airways, a step further in asthma management.

Introduction: During the last decade, small airway (SA) involvement in asthma and Chronic Obstructive Pulmonary Disease (COPD) have reached increasing attention. Originally referred to as the 'silent zone', SA may not be that silent after all. Important clinical correlates are asthma exacerbations and airways remodelling, exercise asthma and nocturnal asthma.

Mast cell-associated alveolar inflammation in patients with atopic uncontrolled asthma.

Background: A significant proportion of patients with asthma have persistent symptoms despite treatment with inhaled glucocorticosteroids.

Objective: We hypothesized that in these patients, the alveolar parenchyma is subjected to mast cell-associated alterations.

Methods: Bronchial and transbronchial biopsies from healthy controls (n = 8), patients with allergic rhinitis (n = 8), and patients with atopic uncontrolled asthma (symptoms despite treatment with inhaled glucocorticosteroids; mean dose, 743 μg/d; n = 14) were processed for immunohistochemical identification of mast cell subtypes and mast cell expression of FcεRI and surface-bound IgE.

Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome.

It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms, which we have called "asthma endotypes.

Comparison of central and peripheral airway involvement before and during methacholine, mannitol and eucapnic hyperventilation challenges in mild asthmatics.

Introduction: Testing for airway hyperresponsiveness with indirect stimuli as exercise or mannitol has been proposed to better reflect underlying airway inflammation, as compared with methacholine (MCh), believed to act directly on airway smooth muscle cells.

Objective: To investigate whether different direct and indirect stimuli induces different patterns of obstruction, recorded as central and peripheral resistance, and to see whether baseline resistance could predict a positive response to direct or indirect provocation.

Methods: Thirty-four mild asthmatics and 15 controls underwent MCh, mannitol and eucapnic voluntary hyperventilation (EVH) challenge tests.

Hyperpnea-induced bronchoconstriction and urinary CC16 levels in athletes.

Purpose: Exercise-induced bronchoconstriction (EIB) is a common condition in both individuals with asthma and otherwise healthy elite athletes. Although excessive water loss by peripheral airways during hyperpnea is regarded as the initial trigger for EIB, the cascade of events that follows remains unclear. Our goal was to establish whether transient disruption of the airway epithelial barrier occurs after a short period of hyperpnea of dry air in athletes with EIB.

Increased alveolar nitric oxide in early systemic sclerosis.

Objectives: Assessment of inflammatory activity in interstitial lung disease of systemic sclerosis (SSc) is difficult. Nitric oxide (NO) has gained attention in the pathogenesis of SSc. The aim of the study was to investigate alveolar NO concentration (CA(NO)) in SSc patients with short disease duration and to relate CA(NO) to radiologic findings.

IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways.

Rationale: IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma.

Objectives: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation.

dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant.

Rationale: Thymic Stromal Lymphopoietin (TSLP) is considered a hub cytokine that activates dendritic cells and T-cells producing asthma-like Th₂-inflammation. Viral stimuli, a major cause of asthma exacerbations, have been shown to induce overexpression of TSLP in asthmatic epithelium. Capsazepine has multiple effects and is of interest because it relaxes human small airways.

Swedish translation and validation of the Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ).

Aim: The aim of the study was to translate and validate the PADQLQ (Pediatric Allergic Disease Quality of Life Questionnaire), a disease-specific quality of life questionnaire for the assessment of quality of life in children with pollen allergy.

Methods: The PADQLQ was translated into Swedish according to guidelines. Children aged 7-18 with grass pollen allergy were included.

Asthma is more prevalent in elite swimming adolescents despite better mental and physical health.

An increased risk of developing asthma has been reported among swimmers exposed to chloramine in pool arenas. The aim of the present study was to compare the prevalence of asthma and respiratory symptoms among elite aspiring swimmers compared with age-matched controls with different degrees of physical activity. We also aimed to relate these findings to mental and psychosocial factors.

Increased cysteinyl-leukotrienes and 8-isoprostane in exhaled breath condensate from systemic sclerosis patients.

Objectives: SSc is a systemic CTD characterized by fibrosis in skin and internal organs. Interstitial lung disease is a frequent complication with fibrosis in the lung parenchyma. The fibrotic process is believed to be influenced by leukotrienes (LTs) and also by oxidative stress.

Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers.

Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress.

Altered matrix production in the distal airways of individuals with asthma.

Background And Aims: Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodelling in central and distal airways.

Methods: Distal and central fibroblasts from controls (n=12) and patients with mild asthma (n=11) were cultured and incubated for 24 h with 0.

Relationship between matrix production by bronchial fibroblasts and lung function and AHR in asthma.

The reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients' lung function and airway hyperreactivity (AHR). Following 24-h fibroblast incubation in 0.

Levels of cysteinyl-leukotrienes in exhaled breath condensate are not due to saliva contamination.

Background And Aims: Saliva contamination has been suggested to be a major contributor to levels of cysteinyl leukotrienes in exhaled breath condensate (EBC). The aim of this study was to compare the levels of cysteinyl-leukotrienes (CysLT) and alpha-amylase activity in EBC to induced sputum and saliva collected from the same subjects (asthmatics and control). We thereby aimed to find out whether saliva contamination could be a plausible explanation to the levels found in EBC or not.

Pathological airway remodelling in inflammation.

Introduction: Airway remodelling refers to a wide pattern of pathophysiological mechanisms involving smooth muscle cell hyperplasia, increase of activated fibroblasts and myofibroblasts with deposition of extracellular matrix. In asthma, it includes alterations of the epithelial cell layer with goblet cell hyperplasia, thickening of basement membranes, peri-bronchial and peri-bronchoalveolar fibrosis. Moreover, airway remodelling occurs not only in asthma but also in several pulmonary disorders such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and systemic sclerosis.

MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function.

Background: Peripheral blood eosinophilia and lung mucosal eosinophil infiltration are hallmarks of bronchial asthma. IL-5 is a critical cytokine for eosinophil maturation, survival, and mobilization. Attempts to target eosinophils for the treatment of asthma by means of IL-5 neutralization have only resulted in partial removal of airway eosinophils, and this warrants the development of more effective interventions to further explore the role of eosinophils in the clinical expression of asthma.

Montelukast in the treatment of asthma and beyond.

Asthma is a chronic inflammatory disease affecting over 300 million people worldwide. The common association with allergic rhinitis and the presence of proinflammatory cells and mediators in the circulation of patients qualify asthma as a systemic disease. This characteristic and the fact that the gold-standard therapy for persistent asthma, inhaled corticosteroids, cannot suppress all components of airway inflammation and fail to adequately penetrate into the small airways, warrant the quest for effective systemic anti-asthma therapies.

Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients.

Objective: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD.

Methods: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300mug or placebo twice daily via Turbuhaler((R)) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured.

Airway hyperresponsiveness to methacholine, adenosine 5-monophosphate, mannitol, eucapnic voluntary hyperpnoea and field exercise challenge in elite cross-country skiers.

Background: Methacholine hyperresponsiveness is prevalent in elite athletes. Comparative studies have hitherto been limited to methacholine, eucapnic voluntary hyperpnoea and exercise. This study investigated airway responsiveness to these stimuli as well as to adenosine 5'-monophosphate (AMP) and mannitol, in 58 cross-country ski athletes.

Altered fibroblast proteoglycan production in COPD.

Background: Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis.