Adenosine and adenosine receptors in the pathomechanism and treatment of respiratory diseases.

It has been known for a long time that inhaled adenosine-monophosphate (AMP) induces airway obstruction in asthmatic patients, but not in healthy subjects. The mechanism of AMP is indirect and occurs via its decay product, adenosine. It stimulates mast cells through its low-affinity receptor A2B to release histamine, which ultimately leads to smooth muscle contraction. This feature of adenosine reveals its pro-inflammatory function, which may play important role in asthma. Indeed, mice lacking adenosine deaminase (ADA), an enzyme which decomposes adenosine, develop asthma-like disorder with elevated IgE, eosinophilia and airway hyperresponsiveness. Human studies showed elevated adenosine levels in bronchoalveolar lavage and exhaled breath condensate of asthmatics as compared to healthy people. Furthermore, certain human ADA phenotypes are associated with prevalence of asthma. These data suggest a protective role for ADA and a pro-inflammatory function for adenosine in asthma. The role of adenosine in inflammatory processes, however, is not unequivocal. Some in vitro studies showed that adenosine binding to its high-affinity receptor A2A results in inhibition of leukotriene synthesis or function of adhesion molecules. It is possible that the concentration of adenosine in lung tissues determines whether it promotes or reduces inflammation. Adenosine has also been associated with other respiratory diseases such as fibrosis, sarcoidosis, cystic fibrosis or tuberculosis. Identification of adenosine receptor subtypes and their role in the pathomechanism of respiratory diseases may provide new therapeutical targets. This review aims to summarize the role of adenosine and adenosine receptors in asthma and other pulmonary disorders.

In vivo platelet activation following myocardial infarction and acute coronary ischaemia.

Forty-seven patients presenting with acute chest pain had in vivo platelet activity assessed by measuring plasma levels of the platelet-specific protein beta thromboglobulin (BTG), and by screening for the presence of circulating platelet aggregates. Nineteen patients with transmural myocardial infarction (MI), 21 patients with acute coronary ischaemia (CI), and 7 patients with non-cardiac chest pain (NCCP) were investigated in a serial study and compared with a normal control group. The means of all BTG determinations in the MI (34, +/- SD = 21-57) and CI (33, +/- SD = 19-57) groups were significantly higher than those in the NCCP group (24, +/- SD equal 17-34; p less than 0.01) and normal subjects (22,5 +/- SD = 14-37; p less than 0.001). There was no difference in BTG between those with MI or CI, nor between the NCCP group and normal subjects. Raised numbers of circulating platelet aggregates could not be detected in either MI or CI. The mean BTG levels in both MI and CI patients were significantly raised, compared to normal subjects, on the first day of admission to hospital and remained so on each of the subsequent nine days. Neither heparin plus warfarin nor sulphinpyrazone had any significant effect in lowering BTG levels. 15/40 patients (37.5%) following MI and CI had repeatedly raised BTG levels throughout the study period, and it is suggested that these patients represent an "at risk" group that may benefit from anti-platelet therapy in secondary prevention studies.

[Condensation of D-glycosamines with proteins]. / Condensation de D-glycosylamines avec des protéines

4-O-beta-D-Galactopyranosyl-alpha,beta-D-glucopyranosylamine (lactosylamine), beta-D-gluco-, alpha- and beta-D-galacto-, and beta-D-manno-pyranosylamines were bound to the carbodiimide-activated carboxyl groups of lysozyme. Of the 11 free carboxyl groups of the protein, approximately 3 were substituted by alpha,beta-lactosylamine, and approximately 2 by the monohexosylamines. One of the 4 glycopeptides isolated from the tryptic digest of the lysozyme-lactosylamine conjugate was identical to synthetic 1-N-L-leucinoyl-4-O-beta-D-galactopyranosyl-beta-D-glucopyranosylamine, indicating the substitution of the carboxyl group of the C-terminal leucine residue. The isolation of a glycopeptide containing the aspartic acid residue in position 117 indicates that the second alpha,beta-lactosylamine residue is linked to the carboxyl group of this amino acid. Both of the 2 other glycopeptides contain the same free carboxyl groups (one glutamic and two aspartic acid residues in positions 35, 48, and 52, respectively). The third alpha,beta-lactosylamine residue seems to be linked to one of these carboxyl groups.

[A case of numerous foreign bodies found in the esophagus and the right main bronchus]. / Nagy mennyiségü idegentestet nyelö és a jobb oldali föhörgöbe aspiráló operált betegünkröl.

The authors report about the elimination of foreign bodies fixed in the oesophagus and aspirated into the right main bronchus. They discuss the diagnostic work and the ways of its elimination. They emphasize the importance of cooperation between the endoscopist and the surgeon.

The effect of allergic rhinitis on adenosine concentration in exhaled breath condensate.

BACKGROUND: Patients with allergic rhinitis (AR) frequently develop asthma. This initiating inflammation in the lower airways may result in increased levels of inflammatory mediators such as adenosine in the exhaled breath. OBJECTIVE: We compared adenosine levels in exhaled breath condensate (EBC) and both exhaled and nasal nitric oxide (NO) levels of AR patients and healthy control subjects. We also tested whether inhalation through inflamed nasal cavity during EBC sampling influences adenosine concentrations in exhaled air. METHODS: Exhaled and nasal NO levels were measured and EBC samples (at oral inhalation) were collected from 27 patients and 15 healthy controls. EBC collection was repeated after 15 min with subjects inhaling through their nose. Adenosine was measured by HPLC and NO was determined by chemiluminescence. RESULTS: The concentration of EBC adenosine was higher in patients with AR than in healthy controls (12.4+/-1.3 nM vs. 6.5+/-0.7 nM, P=0.0019) and this was accompanied by an increase in the concentration of exhaled NO (10.2+/-1.3 ppb vs. 5.3+/-0.5 ppb; P=0.0099, respectively). No difference in nasal NO was detected. EBC adenosine concentration showed a significant positive correlation with the level of exhaled NO. In contrast to healthy control subjects, patients with rhinitis had higher levels of exhaled adenosine when inhaling via the nose instead of the mouth (17.7+/-2.8 nM, P=0.007). CONCLUSION: When compared with healthy subjects, patients with AR exhibit an increased concentration of exhaled adenosine and a related increase in exhaled NO concentration. EBC adenosine is further increased when rhinitis patients inhale through their nose than via their mouth. Our data suggest that non-asthmatic patients with rhinitis may have subclinical inflammation in their lower airways.

Adenosine level in exhaled breath increases during exercise-induced bronchoconstriction.

In asthmatic patients, airway obstruction provoked by exercise challenge is accompanied by an increase in plasma adenosine level. In this study, the current authors investigated if exercise-induced bronchoconstriction was associated with local changes of adenosine concentration in the airways. Oral exhaled breath condensate (EBC) collection (5-min duration) and forced expiratory volume in one second (FEV1) measurements were performed at rest (baseline) and 4-8 times after treadmill exercise challenge in healthy and asthmatic subjects. Adenosine concentration in EBC was determined by HPLC. Observations indicated that physical exercise results in bronchoconstriction together with a significant increase of adenosine level in EBC in asthmatic patients (mean+/-sd maximal fall in FEV1 27+/-13%; associated increase in adenosine 110+/-76% as compared to baseline), but not in healthy control subjects. Exercise-induced changes in adenosine concentration correlated significantly with the fall in FEV1 values in asthmatic patients. In conclusion, the observed increase in adenosine concentration of oral exhaled breath condensate most probably reflects changes in the airways during exercise-induced bronchoconstriction. Due to its known bronchoconstrictor property in asthma, adenosine may contribute to the development of bronchospasm.

Exhaled breath condensate: methodological recommendations and unresolved questions.

Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

How effective is the routine mediastinal blockdissection in the surgery of non-small cell lung cancer?

The performance of ipsilateral mediastinal blockdissection as a routine in every non-small cell lung cancer (NSCLC) operation gives us a chance to judge the accuracy of the preoperative CT examination. The accuracy rate of the CT in our 316 cases was 70.6%, the false positive rate was 69.6%, the false negative rate was 18.2%. Taking into account the 18.2% false negative rate and the slightly better survival of patients operated with routine blockdissection compared to the survival of a group of patients who had mediastinal blockdissection only if suspicion of tumour spread arose, we consider the procedure reasonable in every NSCLC operation.

Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma.

Persistent airway inflammation may require the use of different markers for monitoring airway inflammation. In this study, the authors investigated whether adenosine, which may be produced in allergic inflammatory conditions, could be measured with good reproducibility in exhaled breath condensate (EBC), and whether its concentration was elevated in patients with asthma. EBC adenosine and exhaled nitric oxide (eNO), a noninvasive marker of asthmatic airway inflammation, were measured in 40 healthy volunteers and 43 patients with allergic bronchial asthma. Repeatability of adenosine measurement was checked in 20 pairs of samples collected from healthy control subjects. Adenosine was detectable in all EBC samples by the applied high-performance liquid chromatographic method. The mean difference between repeated measurements of adenosine was -0.1 nM and all differences were within the coefficient of repeatability. Adenosine concentration was higher in steroid-naive patients (n=23) compared with healthy control subjects and steroid-treated patients (n=20). In patients with worsening symptoms of asthma (n=23), adenosine concentration was elevated compared with those in a stable condition (n=20). Furthermore, adenosine concentrations were related to eNO levels in asthmatic patients. These results, showing good reproducibility of adenosine measurements and increased adenosine concentrations in steroid-naive patients and in patients with worsening of asthmatic symptoms, indicate that adenosine measurement in exhaled breath condensate might be an acceptable novel method to investigate the role of local production of adenosine in the airways.