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Objective: Small airway disease and chronic obstructive pulmonary disease are common in primary Sjögren's syndrome (pSS). However, the underlying inflammatory mechanisms behind pSS-associated airway disease have not been studied in detail. We therefore wanted to study cytokine and leucocyte levels in induced sputum in never-smoking patients with pSS.Method: Induced sputum cytokines and leucocytes were assessed in 20 never-smoking patients with pSS and 19 age- and gender-matched population-based controls. In addition, pulmonary function, disease activity, respiratory symptoms, and inflammatory and serological features of pSS were assessed.Results: B-cell activating factor (BAFF), interleukin-6 (IL-6) and IL-8 were significantly increased in induced sputum in pSS patients compared to population-based controls, while IL-1β, interferon-α, and tumour necrosis factor-α levels and leucocytes were not. The proportion of lymphocytes and BAFF levels in induced sputum correlated significantly in pSS patients. However, cytokine levels in induced sputum were not associated with pulmonary function tests, disease activity, respiratory symptoms, or serological features of pSS.Conclusion: The increase in BAFF, IL-6, and IL-8 in induced sputum suggests a specific ongoing inflammatory disease process in the airways in pSS patients. Its association with pSS-associated airway disease needs to be further examined in future larger studies. [ABSTRACT FROM AUTHOR]

Background Allergy and asthma are closely linked. Inhalation of allergen induces an early allergic response ( EAR) within the airways of allergic asthmatic subjects, which is followed by a late allergic response ( LAR) in approximately 50% of the subjects. The LAR is defined as a drop in forced expiratory volume in 1 second ( FEV1) from baseline usually occurring 4-8 hours after exposure and is believed to affect small airways. However, FEV1 is insensitive to changes in small airway physiology. Objective Our aim was to investigate and compare the pathophysiological processes in large and small airways during the EAR and the LAR and to characterize subjects with both an EAR and a LAR (dual responders) versus those with an EAR only (single responders). Methods Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Lung physiology was assessed by spirometry, impulse oscillometry ( IOS), body plethysmography, inert gas washout, single breath methane dilution carbon monoxide diffusion and exhaled breath temperature (EBT), at baseline and repeatedly for 23 hours post-allergen challenge. Results Peripheral airway resistance, air trapping and ventilation heterogeneity were significantly increased in dual responders (n = 15) compared to single responders (n = 19) 6-8 hours post-challenge. Parameters of peripheral airway resistance and ventilation heterogeneity, measured with IOS and inert gas washout, respectively, correlated at baseline and during the allergic airway response in all subjects. Conclusion The LAR involves increased resistance and ventilation defects within the peripheral airways. Alternative definitions of the LAR including small airways pathophysiology could be considered. Clinical relevance Small airway dysfunction during the LAR suggests that dual responders may have more extensive airway pathology and underscores the relevance of small airways assessment in asthma. [ABSTRACT FROM AUTHOR]

Introduction Increased exhaled nitric oxide ( NO) levels in asthma are suggested to be through inducible NO synthase (i NOS). The aim of this study was to investigate the expression of i NOS in bronchoalveolar lavage ( BAL) cells and tissue from central and peripheral airways and compare it with the exhaled bronchial and alveolar NO levels in patients with asthma vs a control group. Methods Thirty-two patients with asthma (defined as controlled or uncontrolled according to Asthma Control Test score cut-off: 20) and eight healthy controls were included. Exhaled NO was measured, and alveolar concentration and bronchial flux were calculated. i NOS was measured in central and peripheral lung biopsies, as well as BAL cells. Bronchoalveolar lavage macrophages were stimulated in vitro, and i NOS expression and NO production were investigated. Results Expression of i NOS was increased in central airway tissue and the alveolar compartment in uncontrolled as compared to controlled asthmatics and healthy controls. There were no differences, however, in i NOS m RNA levels in total BAL cells in uncontrolled as compared to controlled asthma. Bronchoalveolar lavage cell m RNA levels of i NOS or i NOS expression in central and alveolar tissue did not relate to alveolar NO, nor to bronchial flux of NO. In vitro stimulation with leukotriene D4 increased i NOS m RNA levels and NO production in cultured BAL macrophages. Conclusion The levels of both bronchial and alveolar i NOS are increased in uncontrolled as compared to controlled asthma. However, levels of i NOS in BAL macrophages were not reflected by alveolar NO. Both central and distal i NOS levels may reflect responsiveness to steroid treatment. [ABSTRACT FROM AUTHOR]

Objectives: In systemic sclerosis (SSc)-related interstitial lung disease (ILD), elevated eosinophil counts in bronchoalveolar lavage are associated with a worse outcome. We hypothesized that eosinophils may be activated in the peripheral circulation, thereby increasing their recruitment to affected tissues and contributing to inflammation and fibrosis. The aim of this study was to characterize the blood eosinophils in SSc patients. Method: Expression levels of surface markers CD11b, CD44, CD48, CD54, CD69, CD81, and HLA-DR on CD16(low)CD9(high)-expressing eosinophils were measured by flow cytometry in whole blood from SSc patients (n = 32) and controls (n = 11). Results: Expression levels of CD54, CD69, and HLA-DR were undetectable in all groups. CD44 and CD11b expression levels were similar between groups. CD81 expression was lower in patients compared to controls independent of disease duration (p = 0.001). CD48 expression was increased in patients with a short disease duration (< 2 years) compared to both controls (p = 0.042) and patients with longer disease duration (≥ 2 years; p = 0.027). In patients with short disease duration, increased CD48 expression was associated with alveolar inflammation as measured by an increased concentration of alveolar nitric oxide (r = 0.76, p = 0.003). Conclusions: Blood eosinophils change phenotype during disease evolution in SSc, and CD48 expression may be used as a biomarker for pulmonary inflammation. [ABSTRACT FROM AUTHOR]

Repeated injury of the airway epithelium caused by hyperpnoea of poorly conditioned air has been proposed as a key factor in the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. In animals, the short-acting β2-agonist terbutaline has been shown to reduce dry airflow-induced bronchoconstriction and the associated shedding of airway epithelial cells. Our aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea-induced bronchoconstriction and airway epithelial injury in athletes. Twentyseven athletes with EIB participated in a randomized, double-blind, placebo-controlled, crossover study. Athletes completed an 8-min eucapnic voluntary hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5 mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of airway epithelial perturbation) were measured before and up to 60 min after EVH. The maximum fall in FEV1 of 17 ± 8% (SD) on placebo was reduced to 8 ± 5% following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post-EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly reduced this rise (pre- to postchallenge CC16 increase 416 ± 495 pg/μmol creatinine after placebo vs. 315 ± 523 pg/μmol creatinine after terbutaline, P = 0.016). These results suggest that the inhalation of a single therapeutic dose of terbutaline offers significant protection against hyperpnoeainduced bronchoconstriction and attenuates acute airway epithelial perturbation in athletes. [ABSTRACT FROM AUTHOR]

Objective: To study serum type I interferon (IFN) activity in patients with early systemic sclerosis (SSc). Method: Serum type I IFN activity was measured in 33 consecutive patients with SSc and a disease duration of < 2 years and in 13 healthy individuals by calculating a type I IFN score according to the induction of six IFN-α regulated genes in a reporter cell line. Results: Twenty-seven per cent of the SSc patients had an increased type I IFN score compared to none of the healthy individuals (p < 0.05). The clinical SSc phenotype associated with high serum type I IFN activity did not differ from patients with low serum type I IFN activity regarding the presence of skin or lung fibrosis, pulmonary hypertension, or digital complications. Patients with high serum type I IFN activity were younger (p < 0.01) and had a lower frequency of cardiac involvement (p = 0.053), lower leucocyte count (p < 0.001), higher immunoglobulin (Ig)G levels (p < 0.05), and a higher amount of antibodies against extractable nuclear antigens (p < 0.01) than patients with low serum type I IFN activity. The presence of antibodies against topoisomerase I, Sjögren's syndrome antigen, and nuclear ribonucleoprotein antigens was associated with higher type I IFN activity (p < 0.05 for all comparisons). Conclusions: Our study indicates that increased serum type I IFN activity in early SSc patients is associated with an antibody and laboratory profile that may reflect a subclinical overlap of SSc with other type I IFN-driven connective tissue diseases (CTDs). [ABSTRACT FROM AUTHOR]

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. One hundred and one elite swimmers and 1628 age-matched controls answered a questionnaire containing questions about respiratory symptoms, lifestyle factors, mental and physical well-being. The controls were divided into three different groups according to the degree of physical activity, no physical activity, recreational training and elite training. Swimmers reported significantly more asthma symptoms, with 36.6% having physician-diagnosed asthma, compared with 16.2% among the controls. Use of regular medication was more common (14.9% vs 8.0%) and more swimmers reported an exacerbation of their asthma during the previous 12 months (16.8%) vs (5.8%) for the controls. Despite an increased prevalence of asthma symptoms, the swimmers reported best physical performance and best mental and physical well-being. They also had a healthier lifestyle without smoking and low alcohol consumption. [ABSTRACT FROM AUTHOR]

To cite this article: Andersson CK, Tufvesson E, Aronsson D, Bergqvist A, Mori M, Bjermer L, Erjefält JS. Alveolar mast cells shift to an FcεRI-expressing phenotype in mild atopic asthma: a novel feature in allergic asthma pathology. Allergy 2011; 66: 1590-1597. Abstract Background: A unique feature of alveolar mast cells is their low high-affinity IgE receptor (FcεRI) expression. Recent discoveries in uncontrolled asthma suggest that the appearance of FcεRI-expressing alveolar mast cells may be a novel disease-specific feature of allergic asthma. This study investigates whether increased FcεRI-expressing alveolar mast cells are present in patients with mild allergic asthma or even in non-asthmatic allergic rhinitis patients (AR) who have developed bronchial hyperactivity (BHR). Methods: Bronchial and alveolar tissues were obtained from healthy controls, AR patients with or without BHR, and AR patients with concurrent asthma. Samples were processed for immunohistochemical identification of MCT and MCTC and expression of FcεRI and surface-bound IgE. Results: Bronchial mast cell expression of FcεRI was high in all groups. In contrast, in the alveolar tissue, the expression of FcεRI on mast cells was low in healthy controls and in the AR patient groups, whereas a high expression was present in AR patients with concurrent asthma ( P = 0.006 compared to controls). The asthmatics had a 29-fold increase in numbers ( P = 0.006) and a 19-fold increase in proportion ( P = 0.007) of alveolar mast cells that expressed surface-bound IgE. Conclusions: The present data show that alveolar mast cells in patients with mild atopic asthma, but not atopic patients with AR, have turned into a highly FcεRI- and IgE-expressing phenotype. These data support the hypothesis that increased FcεRI expression on alveolar mast cells is a novel disease-specific feature of allergic asthma that is important for understanding asthma phenotypes and designing new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Injury to the airway epithelium has been proposed as a key susceptibility factor for exercise-induced bronchoconstriction (EIB). Our goals were to establish whether airway epithelial cell injury occurs during EIB in athletes and whether inhalation of warm humid air inhibits this injury. Twenty-one young male athletes (10 with a history of EIB) performed two 8-min exercise tests near maximal aerobic capacity in cold dry (4°C, 37% relative humidity) and warm humid (25°C, 94% relative humidity) air on separate days. Postexercise changes in urinary CC16 were used as a biomarker of airway epithelial cell perturbation and injury. Bronchoconstriction occurred in eight athletes in the cold dry environment and was completely blocked by inhalation of warm humid air [maximal fall in forced expiratory volume in 1 s = 18.1 ± 2.1% (SD) in cold dry air and 1.7 ± 0.8% in warm humid air, P < 0.01 ]. Exercise caused an increase in urinary excretion of CC16 in all subjects (P < 0.001), but this rise in CC16 was blunted following inhalation of warm humid air [median CC 16 increase pre- to postchallenge = 1.91 and 0.35 ng/µmol in cold dry and warm humid air, respectively, in athletes with EIB (P = 0.017) and 1.68 and 0.48 ng/µmol in cold dry and warm humid air, respectively, in athletes without EIB (P = 0.002)]. The results indicate that exercise hyperpnea transiently disrupts the airway epithelium of all athletes (not only in those with EIB) and that inhalation of warm moist air limits airway epithelial cell perturbation and injury. [ABSTRACT FROM AUTHOR]

Background We have previously reported that asthma differs from rhinitis with or without bronchial hyperresponsiveness in the perception and degree of lower airway inflammation. Objective The aim of the present study was to investigate whether sputum levels of inflammatory markers could further distinguish these patient groups. Methods Patients with seasonal allergic rhinitis with or without asthma or bronchial hyperresponsiveness to methacholine were investigated. Induced sputum was performed during as well as off season, and analysed for cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other inflammatory markers. Results Asthmatic patients differentiated from those with rhinitis with or without bronchial hyperresponsiveness in levels of cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%–upper 95% confidence interval (CI) of geometric mean: 1.9–5.1) vs. 1.4 (0.9–2.2) and 0.7 (0.3–1.6) pg/μg total protein] and hyaluronan [0.30 (0.22–0.43) vs. 0.15 (0.10–0.20) and 0.20 (0.12–0.35) ng/μg total protein] in sputum. The levels of cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the levels of hyaluronan remained elevated off-season. Furthermore, elevated levels of ECP were noticed among both the asthmatic and rhinitis patients with hyperresponsiveness compared with controls [0.022 (0.014–0.033) and 0.015 (0.011–0.021) compared with 0.010 (0.007–0.014) ng/μg total protein]. The level of ECP remained elevated off season. Conclusion Cysteinyl-leukotrienes are possibly more related to mast cell-mediated inflammation and remodelling, also indicated by increased levels of hyaluronan during and off season. This inflammation may be partly different from the eosinophil-driven inflammation. [ABSTRACT FROM AUTHOR]

Background/aim Allergic rhinitis (AR) is a risk factor for developing clinical asthma. Moreover, AR is often associated with bronchial hyper-responsiveness (BHR). The aim of the present study was to investigate whether patients with AR and asthma differed from AR with or without BHR in degree of perception of dyspnoea and airway inflammation, measured as fractionated exhaled nitric oxide (NO). Materials Twenty-nine patients with seasonal AR (timothy) were investigated with metacholine challenge test. Fourteen healthy non-reactive subjects served as controls. Methods (1) Metacholine challenge test, cut-off value forced expiratory volume in 1 s (FEV1) PD20 2000 μg. Slope value for metacholine was calculated as %fall in FEV1/mol metacholine. Dyspnoea during challenge was measured with a 10-graded modified Borg score. (2) Measurement of fractional-exhaled nitric oxide (FENO) at flow rate 50 mL/s. Results Eighteen patients reported AR only, without asthma symptoms, and 12 (67%) were BHR. Eleven subjects had both rhinitis and asthma symptoms. Patients with rhinitis and asthma reported significantly more dyspnoea per percent fall in FEV1 compared with those with rhinitis and BHR. Moreover, those with rhinitis and asthma had significantly higher NO values compared with those with rhinitis and BHR. Conclusion The difference between rhinitis patients with or without asthma symptoms seems to be mainly a question of perception of dyspnoea. However, FENO measurement indicates that dyspnoea may also be associated with increased inflammatory activity in the peripheral airways. [ABSTRACT FROM AUTHOR]