The role of endogenous and exogenous AMP in asthma and chronic obstructive pulmonary disease

Berge, Maarten van den; Polosa, Riccardo; Kerstjens, Huib A. M.; Postma, Dirkje S.

doi:10.1016/j.jaci.2004.05.071

Cited by 47 publications

(31 citation statements)

References 101 publications

(100 reference statements)

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“…Clinical studies in asthma patients have shown that AHR to AMP reflects an underlying eosinophilic or atopic airway inflammation more accurately than AHR to methacholine [21,26]. This hypothesis is supported by the current authors' observation of a positive correlation between blood eosinophil counts and AMP PC20, but not between blood eosinophil counts and methacholine PC20 in the asthma group.…”

Section: Discussionsupporting

confidence: 73%

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans

Yoo

Kim

et al. 2006

European Respiratory Journal

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Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO).Methacholine and adenosine 59-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n528). These results were compared with those of asthmatic (n530) and control children (n525).Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) of ,16 mg?mL -1 , but only six (21.4%) were hyperreactive to AMP with a PC20of ,200 mg?mL -1. All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges.Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 59-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects.

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Section: Discussionsupporting

confidence: 73%

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans

Yoo

Kim

et al. 2006

European Respiratory Journal

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“…The present results suggest that ATP release during airway inflammation has two major functions: (1) it promotes an acute defense mechanism by increasing mucociliary clearance; and (2) it induces an immune response by activation of mast cell degranulation [5,17,18]. In a recent study, Idzko et al supplied evidences that ATP is an important mediator in the pathogenesis of asthma.…”

Section: Discussionsupporting

confidence: 55%

Allergen-induced airway hyperresponsiveness is absent in ecto-5′-nucleotidase (CD73)-deficient mice

Schreiber

Castrop

Kunzelmann

2008

Pflugers Arch - Eur J Physiol

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Adenosine is formed from extracellular purines by ecto-5'-nucleotidase (CD73) and is an essential player in allergic airway inflammation. The contribution of adenosine and other purines to electrolyte transport and mucociliary clearance was studied in airways of allergen challenged mice. No signs for allergen-induced inflammation were found in CD73-/- mice, and adenosine monophosphate (AMP) was unable to elicit airway Cl(-) secretion in these animals. Tracheas of ovalbumin (OVA)-treated BALB/c and CD73+/+ mice were hyperresponsive towards methacholine when assessed by Penh and direct optical measurement of contraction. In addition Cl(-) secretion activated by ATP and ADP was enhanced. These changes were not observed in CD73-/- mice. Expression of CFTR or CLCA was unchanged upon OVA treatment of CD73 mice, suggesting enhanced Cl(-) secretion due to upregulated purinergic pathways. Mucociliary clearance was determined by measuring particle transport in excised mouse tracheas and was strongly enhanced in OVA-challenged CD73+/+ mice, but remained unchanged in CD73-/- mice. While mucociliary clearance is activated by allergen exposure independent of functional ecto-5'-nucleotidase, airway inflammation is largely dependent on CD73. Thus, ecto-5'-nucleotidase may provide a novel target for therapeutic intervention, probably by local application of ecto-5'-nucleotidase inhibitors through inhalation.

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“…Therefore, the current findings provide the first evidence that AMP inhalation has a late effect on airway neutrophil migration in asthmatics. There is evidence that AMP challenge may provoke cellular chemoattraction within the airways through the release of a variety of inflammatory mediators from lung mast cells, namely LTB 4 , IL-5, IL-8 and tumour necrosis factor-a, all chemoattractants for neutrophils [12,26]. The percentage of neutrophils did not correlate with IL-8 in the present study, possibly because the latter measurements were not sufficiently sensitive or other unmeasured mediators and/or receptors could have been involved.…”

Section: Induced Sputum Findingscontrasting

confidence: 65%

Adenosine 5'-monophosphate in asthma: gas exchange and sputum cellular responses

Manrique

Gómez²,

Muñoz³

et al. 2008

European Respiratory Journal

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Adenosine 59-monophosphate (AMP) bronchoprovocation reproduces the lung function abnormalities that occur spontaneously during acute asthma and detects peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone.The present authors investigated whether AMP induced a greater imbalance in the ventilation/ perfusion ratio than methacholine (MCh), at an equivalent degree of bronchoconstriction, with and without salbutamol pre-medication. In total, 36 asthmatics were studied in three randomised, doubleblind, crossover studies: 1) before and after AMP or MCh; 2) before and 30 min after salbutamol or placebo, followed by AMP; or 3) MCh challenge. Sputum was collected before and 4 h post-challenge.Compared with MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (forced expiratory volume in one second decrease of 28-44%). While salbutamol blocked AMP-or MCh-induced bronchoconstriction, arterial oxygen tension (Pa,O 2 ) and alveolar-arterial oxygen tension difference (PA-a,O 2 ) disturbances induced by AMP and MCh were only partially blocked (Pa,O 2 by 46 and 42%, respectively; PA-a,O 2 by 58 and 57%, respectively). Compared with MCh, AMP increased the percentage of neutrophils (mean¡SE increased from 28¡4% to 38¡4%), but this increase did not occur after salbutamol pre-treatment.Both adenosine 59-monophosphate and methacholine induced similar peripheral airway dysfunction. The fully inhibited adenosine 59-monophosphate-induced neutrophilia with residual hypoxaemia observed after salbutamol treatment is probably related to b 2 -agonists acting on both bronchial and pulmonary circulation.

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The role of endogenous and exogenous AMP in asthma and chronic obstructive pulmonary disease

Cited by 47 publications

References 101 publications

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans

Allergen-induced airway hyperresponsiveness is absent in ecto-5′-nucleotidase (CD73)-deficient mice

Adenosine 5'-monophosphate in asthma: gas exchange and sputum cellular responses

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