Search

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The aim of this study was to investigate heterogenic ventilation in the acinar (Sacin) and conductive (Scond) airways of patients with varying chronic obstructive pulmonary disease (COPD) severity and how these relates to advanced lung function parameters, primarily measured by impulse oscillometry (IOS). A secondary aim was to investigate the effects of a short acting beta2-agonist and a muscarinic antagonist on the heterogenic ventilation. Eleven never smoking controls, 12 smoking controls, and 57 COPD patients (7 GOLD 1, 25 GOLD 2, 14 GOLD 3 and 11 GOLD 4) performed flow-volume spirometry, IOS, body plethysmography, single breath carbon monoxide diffusion, and N2-multiple breath washout. Six smoking controls and 13 of the COPD patients also performed double reversibility test by using salbutamol and its combination with ipratropium. Sacin was significantly higher in GOLD 2-4 compared to never smoking controls and smoking controls, but showed similar levels in GOLD 3 and 4. A factor analysis identified 4 components consisting of; 1) IOS parameters, 2) volume parameters, 3) diffusion parameters, Sacin and some IOS parameters and 4) Scond with central obstruction/air trapping. Salbutamol and its combination with ipratropium had no effect on Sacin and Scond. Increased Sacin in COPD was strongly related to diffusion capacity and lung volumes, but also weakly to resistance and reactance, showing a link between ventilation heterogeneity in the acinar airways and parameters measured by IOS., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Airway epithelial injury is regarded as a key contributing factor to the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. The concentration of the pneumoprotein club cell (Clara cell) CC16 in urine has been found to be a non-invasive marker for hyperpnoea-induced airway epithelial perturbation. Exercise-hyperpnoea induces mechanical, thermal and osmotic stress to the airways. We investigated whether osmotic stress alone causes airway epithelial perturbation in athletes with suspected EIB. Twenty-four recreational summer sports athletes who reported respiratory symptoms on exertion performed a standard eucapnic voluntary hyperpnoea test with dry air and a mannitol test (osmotic challenge) on separate days. Median urinary CC16 increased from 120 to 310 ρg μmol creatinine(-1) after dry air hyperpnoea (P = 0.002) and from 90 to 191 ρg μmol creatinine(-1) after mannitol (P = 0.021). There was no difference in urinary CC16 concentration between athletes who did or did not bronchoconstrict after dry air hyperpnoea or mannitol. We conclude that, in recreational summer sports athletes with respiratory symptoms, osmotic stress per se to the airway epithelium induces a rise in urinary excretion of CC16. This suggests that hyperosmolarity of the airway surface lining perturbs the airway epithelium in symptomatic athletes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Exercise is known to affect the airway epithelium through dehydration, followed by a release of mediators, such as club cell (Clara) protein (CC16). The aim of this study was to follow the CC16 levels at repeated time points in plasma and urine after exercise in asthmatic subjects and controls, and to relate the findings to exhaled breath temperature (EBT) and exhaled nitric oxide (NO). Twenty-two asthmatics and 18 healthy subjects performed an exercise challenge test on a treadmill. Lung function, CC16 in plasma and urine, EBT and fractional exhaled NO were investigated before and repeatedly for 60 min after the exercise. The increase in CC16 concentration in plasma was seen already one minute after exercise (p < 0.001) and increased further after 20 (p = 0.009) until 60 min (p = 0.001). An increase in urinary levels of CC16 peaked after 30 min (p < 0.001), and declined after 60 min but were still higher than baseline (p = 0.002). There were no differences in plasma or urine CC16 levels between asthmatics and controls, but males had higher plasma levels compared to females (p < 0.001) at all time points. EBT peaked at 15 min (p < 0.001) and thereafter declined, and FENO50 (p < 0.0001), alveolar NO concentration (p = 0.049) and bronchial flux of NO (p = 0.0055) decreased after exercise. In conclusion, this study shows that CC16 in plasma increased during 60 min after exercise, not synchronized with CC16 levels in urine. CC16 levels in plasma correlated to EBT and exhaled NO, reflecting an overall epithelial involvement. There was no difference between asthmatics and healthy controls, showing a physiological rather than pathophysiological response., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: The aim of the study was to investigate the prevalence of asthma with or without exercise induced symptoms among elite and elite aspiring swimmers and to compare sport specific exercise provocation with mannitol provocation., Methods: 101 adolescent swimmers were investigated with mannitol provocation and sport specific exercise challenge test. Mannitol positivity was defined as either direct FEV(1) PD15 (ordinary criteria) or as β(2)-reversibility ≥15% after challenge (extended criteria). A direct positive exercise test was defined as a drop in FEV(1) of 10% (ordinary criteria) or a difference in FEV of ≥15% either spontaneous, variability, or with β2-agonist, reversibility (extended criteria)., Results: We found a high prevalence of mannitol and/or exercise positivity. Twenty-six swimmers were mannitol direct positive and 14 were direct exercise positive using ordinary criteria. Using extended criteria 43 were mannitol positive and 24 were exercise positive. When including reversibility and variability to define a positive test the sensitivity for current asthma with or without exercise induced symptoms increased while the specificity remained roughly unchanged. Direct positivity for mannitol and exercise poorly overlapped using ordinary criteria but improved using extended criteria., Conclusion: We found a high prevalence of asthma among elite swimmers. The use of variability and reversibility (liability) as additional criteria to define a positive test provided to our mind relevant information and should be considered., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Allergic rhinitis is a predisposing factor for developing clinical asthma. Moreover, allergic rhinitis is often associated with bronchial hyperresponsiveness (BHR). We hypothesise that patients with asthma have more small airway involvement than those with allergic rhinitis and BHR alone. The aim of this study was to assess peripheral and proximal NO concentration in rhinitic subjects, and to correlate the peripheral NO concentration to the peripheral obstruction in response to methacholine. Patients with allergic rhinitis with or without BHR, or clinical asthma were investigated in and out of the allergy season. Healthy subjects served as controls. Fractional exhaled NO was performed, and peripheral NO concentration and proximal flux of NO was calculated. Methacholine test was performed including impulse oscillometry. Rhinitic patients with asthma demonstrate an increase in both proximal and peripheral NO compared to those with rhinitis alone or those with BHR. There is a trend of increased peripheral NO from patients with rhinitis only, rhinitis and BHR, to rhinitis with asthma. The increase in peripheral NO correlated with an increased peripheral obstruction in response to methacholine. Patients with seasonal allergic rhinitis demonstrated a decrease in both proximal and peripheral NO in the off-season. The results support our hypothesis that rhinitic patients with asthma have more peripheral lung inflammation and small airway involvement compared to rhinitic patients with BHR alone.

Background: Exhaled breath condensate (EBC) is simple to collect and as such a non-invasive method that has attracted substantial interest in the last few years. However, several methodological concerns have been raised and it has been difficult to reproduce results between different centres. Because of low concentrations of inflammatory markers, potential loss in the sampling system may have great influence. The aim of the present study was to se if evaporation and plastic coating could facilitate detection., Methodology: Through methodological improvements, we have now made it possible to measure EBC concentrations of eicosanoids and cytokines in our system. Due to absorbance of both fatty acid derivates and proteins to several plastics, the first step is coating of all surfaces with bovine serum albumin and Tween 20. Since several assays are sensitive to these factors, the methodology has to be standardised to avoid false results. Secondly, larger amounts of EBC have to be vacuum-dried, and thereafter resolved in the respective assay buffers. The EBCs have to be concentrated 5-10 times, depending on samples and assay sensitivity., Results: Due to these improvements we can measure, for example, cysteinyl-leukotrienes, leukotriene B4, prostaglandin E and 8-isoprostane. High sensitivity assays have also made it possible to measure cytokines, for example, interleukin (IL)-1beta, IL-8 and IL-13., Summary: We are aware of different results from other labs. However, it seems essential to coat and to concentrate the samples in order to achieve reliable and measurable results.