Lipid-laden alveolar macrophages and pH monitoring in gastroesophageal reflux-related respiratory symptoms

Lipid-laden alveolar macrophages and pH monitoring have been used in the diagnosis of chronic aspiration in children with gastroesophageal reflux (GER). This study was conducted to prove a correlation between the detection of alimentary pulmonary fat phagocytosis and an increasing amount of proximal gastroesophageal reflux. It was assumed that proximal gastroesophageal reflux better correlates with aspiration than distal GER. Patients from 6 months to 16 years with unexplained recurrent wheezy bronchitis and bronchial hyperreactivity, or recurrent pneumonia with chronic cough underwent 24-hour double-channel pH monitoring and bronchoscopy with bronchoalveolar lavage (BAL). Aspiration of gastric content was determined by counting lipid laden alveolar macrophages from BAL specimens. There were no correlations between any pH-monitoring parameters and counts of lipid-laden macrophages in the whole study population, even when restricting analysis to those with abnormal reflux index expressing clinically significant GER. Quantifying lipid-laden alveolar macrophages from BAL in children with gastroesophageal-related respiratory disorders does not have an acceptable specificity to prove chronic aspiration as an underlying etiology. Therefore, research for other markers of pulmonary aspiration is needed

Omega-3 polyunsaturated fatty acids and bronchial inflammation in grass pollen allergy after allergen challenge

SummaryRatioAsthma is a major public health problem, with bronchial inflammation as the therapeutic target. The role of dietary fish oil derived polyunsaturated fatty acids (PUFAs) in allergic inflammation is controversial. Most asthmatics suffer from mild disease and non-pharmacologic interventions are attractive. This study investigates the anti-inflammatory potential of nutritional PUFAs in an experimentally induced bronchial inflammation.MethodsWe examined 38 grass pollen allergic asthmatics and 19 controls. History of dietary PUFA intake was compared with levels of PUFAs in erythrocyte membranes, and stratified according to low (25th quartile; Q25) and high (75th quartile; Q75) ratios of omega-3 (n-3) to omega-6 (n-6) PUFAs as a surrogate for anti-inflammatory (Q75) or proinflammatory (Q25) effects. Bronchial inflammation was simulated with one-step inhalation of grass pollen. Bronchial response (exhaled nitric monoxide, eNO as surrogate for inflammation, decrease of FEV1) was correlated with levels of PUFAs in erythrocyte membranes.ResultsRatios of n-3/n-6 PUFA were significantly lower in asthmatics than in healthy controls. Levels of eNO were significantly higher in Q25 asthmatics than in Q75 asthmatics (p = 0.040). There was a trend of higher bronchial hyperreactivity in Q25 asthmatics (median PD20 0.27 vs. 0.14; n.s.), induced by specific bronchial challenge with grass pollen (FEV1 decrease 16.7 vs. 23.1%; n.s.).ConclusionWhen stratifying for erythrocyte membrane PUFA content as a surrogate for alimentary intake, we found mild effects on bronchial allergic inflammation. Future intervention studies with pharmacological PUFA doses appear suitable to clarify dietary PUFA role as an adjunctive intervention to the established treatment of asthma.ClinicalTrials.gov No. NCT00519740

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Background No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks. Results 26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O 2 -saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O 2 -saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ. Conclusions Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013)

Actions at Neuromuscular and Esteratic Cholinoceptive Sites-of Some Phenylene Diacryloyl Bis-Cholinium Esters1

ABSTRAC

Global modelling of soil carbonyl sulfide exchanges

International audienceCarbonyl sulfide (COS) is an atmospheric trace gas of interest for C cycle research because COS uptake by continental vegetation is strongly related to terrestrial gross primary productivity (GPP), the largest and most uncertain flux in atmospheric CO2 budgets. However, to use atmospheric COS as an additional tracer of GPP, an accurate quantification of COS exchange by soils is also needed. At present, the atmospheric COS budget is unbalanced globally, with total COS flux estimates from oxic and anoxic soils that vary between -409 and -89 GgS yr(-1). This uncertainty hampers the use of atmospheric COS concentrations to constrain GPP estimates through atmospheric transport inversions. In this study we implemented a mechanistic soil COS model in the ORCHIDEE (Organising Carbon and Hydrology In Dynamic Ecosystems) land surface model to simulate COS fluxes in oxic and anoxic soils. Evaluation of the model against flux measurements at seven sites yields a mean root mean square deviation of 1.6 pmolm(-2)s(-1), instead of 2 pmol m(-2)s(-1) when using a previous empirical approach that links soil COS uptake to soil heterotrophic respiration. However, soil COS model evaluation is still limited by the scarcity of observation sites and long-term measurement periods, with all sites located in a latitudinal band between 39 and 62 degrees N and no observations during wintertime in this study. The new model predicts that, globally and over the 2009-2016 period, oxic soils act as a net uptake of -126 GgS yr(-1) and anoxic soils are a source of +96 GgS yr(-1), leading to a global net soil sink of only -30 GgS yr(-1), i.e. much smaller than previous estimates. The small magnitude of the soil fluxes suggests that the error in the COS budget is dominated by the much larger fluxes from plants, oceans, and industrial activities. The predicted spatial distribution of soil COS fluxes, with large emissions from oxic (up to 68.2 pmol COS m(-2) s(-1)) and anoxic (up to 36.8 pmol COS m(-2) S-1) soils in the tropics, especially in India and in the Sahel region, marginally improves the latitudinal gradient of atmospheric COS concentrations, after transport by the LMDZ (Laboratoire de Meteorologie Dynamique) atmospheric transport model. The impact of different soil COS flux representations on the latitudinal gradient of the atmospheric COS concentrations is strongest in the Northern Hemisphere. We also implemented spatiotemporal variations in near-ground atmospheric COS concentrations in the modelling of biospheric COS fluxes, which helped reduce the imbalance of the atmospheric COS budget by lowering soil COS uptake by 10 % and plant COS uptake by 8 % globally (with a revised mean vegetation budget of -576 GgS yr(-1) over 2009-2016). Sensitivity analyses highlighted the different parameters to which each soil COS flux model is the most responsive, selected in a parameter optimization framework. Having both vegetation and soil COS fluxes modelled within ORCHIDEE opens the way for using observed ecosystem COS fluxes and larger-scale atmospheric COS mixing ratios to improve the simulated GPP, through data assimilation techniques

Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients

Patients with interstitial lung disease due to surfactant protein C (SFTPC) mutations are rare and not well characterised. We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations. 17 patients (seven male) were followed over a median of 3 years (range 0.3-19). All patients were heterozygous carriers of autosomal dominant SFTPC mutations. Three mutations (p.L101P, p.E191 K and p.E191*) have not been described before in the context of surfactant protein C deficiency. Patients with alterations in the BRICHOS domain of the protein (amino acids 94-197) presented earlier. At follow-up, one patient was healthy (2 years), six patients were "sick-better" (2.8 years, range 0.8-19), seven patients were "sick-same" (6.5 years, 1.3-15.8) and three patients were "sick-worse" (0.3 years, 0.3-16.9). Radiological findings changed from ground-glass to increasing signs of fibrosis and cyst formation with increasing age. Empiric treatments had variable effects, also in patients with the same genotype. Prospective studies with randomised interventions are urgently needed and can best be performed in the framework of international registers