Effects of Aerosolized Adenosine 5′-Triphosphate vs Adenosine 5′-Monophosphate on Dyspnea and Airway Caliber in Healthy Nonsmokers and Patients With Asthma

doi:10.1378/chest.128.4.1905

Chest

Volume 128, Issue 4, October 2005, Pages 1905-1909

https://doi.org/10.1378/chest.128.4.1905 Get rights and content

Study objectives

Extracellular adenosine 5′-triphosphate (ATP) causes neurogenic bronchoconstriction, inflammation, and coughs, and may play a mechanistic role in obstructive airway diseases. The aims of this study were to determine the effects of inhaled ATP on airway function, and to compare these effects with those of adenosine 5′-monophosphate (AMP).

Design

Prospective, randomized, double-blind study.

Setting

Clinical research laboratory of a postgraduate teaching hospital.

Methods

The effects of inhaled equimolar doses of ATP and AMP on airway caliber, perception of dyspnea quantified by the Borg score, and other symptoms were determined in 10 nonsmokers (age 41 ± 3 years) and 10 patients with asthma (age 39 ± 3 years) [± SEM].

Results

None of the healthy nonsmokers responded to ATP or AMP. All the patients with asthma responded to ATP, and 90% responded to AMP. The geometric mean of the provocative dose causing a 20% fall in FEV₁ (PD₂₀) of ATP was 48.7 μmol/mL and that of PD₂₀ AMP was 113.5 μmol/mL in responsive asthmatics (p < 0.05). In asthmatic patients, the percentage change in FEV₁ caused by ATP was greater than that caused by AMP (ΔFEV₁ ATP = 29% vs ΔFEV₁ AMP = 22%, p < 0.05). Borg score increased significantly in asthmatics after ATP (from 0.1 to 3.3, p < 0.01) and after AMP (from 0.2 to 2.5, p < 0.01). This increase was also greater after ATP than AMP in asthma (ΔBorg ATP = 3.2 vs ΔBorg AMP = 2.3, p < 0.05). ATP induced cough in 16 subjects (80%), while AMP induced cough in 8 subjects (40%) [p < 0.05]; in addition, more subjects had throat irritation after inhalation of ATP than AMP (p < 0.05).

Conclusions

ATP is a more potent bronchoconstrictor and has greater effects on dyspnea and other symptoms than AMP in asthmatic patients. Therefore, ATP could potentially be used as a bronchoprovocator in the clinical setting.

Section snippets

Patients

Healthy nonsmokers (41 ± 3 years old [± SEM], n = 10) and patients with intermittent asthma (Global Initiative for Asthma guidelines) [39 ± 3 years old, n = 10] were studied (Table 1). Healthy nonsmokers had a normal chest examination, normal lung function without reversibility, and no history of any respiratory disorder. Asthmatic patients were clinically stable and free from respiratory tract infection or use of steroids during 4 weeks preceding the study. They were subjected to methacholine

Airway Responsiveness to AMP and ATP

None of the healthy nonsmokers responded to either ATP or AMP. All patients with asthma responded to ATP, whereas 90% of them responded to AMP, ie, showing a ≥ 20% fall in FEV₁ up to the maximal concentrations administered. The geometric mean PD₂₀ ATP was 48.7 μmol/mL (26.9 mg/mL) and PD₂₀ AMP was 113.5 μmol/mL (39.6 mg/mL) in responsive subjects (p < 0.05) [Fig 1].

ATP-induced bronchoconstriction expressed as a percentage of the baseline FEV₁ (ΔFEV₁) was greater than that caused by AMP

Discussion

The present data show that ATP is a more potent bronchoconstrictor and has greater effect on dyspnea and other symptoms than AMP in asthmatic patients. Furthermore, there was a significant relationship between acute changes in airway caliber and Borg score with both ATP and AMP challenges.

All patients with asthma, who were not current smokers, responded to ATP, and 90% of them were AMP responsive. Also, ATP was 2.3-fold more potent than AMP in asthmatic patients as a bronchoconstrictor. The

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In addition, it had been demonstrated using inhalation challenge studies that ATP can produce urge to cough as well as objectively measured increases in cough frequency and with a potency greater than that associated with similar effects of adenosine, a breakdown product of ATP that has also demonstrated the propensity to activate respiratory sensory nerves. Similar findings were made also in regard to bronchospastic responses to the same provocation agents in these studies (Basoglu et al., 2005). This protussive feature of ATP was activated more sensitively in patients with chronic airways diseases (e.g., asthma), the inference being that ATP may trigger or facilitate this cough sensitivity.
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This study was supported by Duska Scientific Co., Bala Cynwyd, PA.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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Chest

Clinical Investigations ASTHMAEffects of Aerosolized Adenosine 5′-Triphosphate vs Adenosine 5′-Monophosphate on Dyspnea and Airway Caliber in Healthy Nonsmokers and Patients With Asthma

Study objectives

Design

Setting

Methods

Results

Conclusions

Section snippets

Patients

Airway Responsiveness to AMP and ATP

Discussion

Bronchoprovocation testing

Clin Chest Med

Adenosine 5′-triphosphate axis in obstructive airway diseases

Am J Ther

ATP modulates anti-IgE-induced release of histamine from human lung mast cells

Am J Respir Cell Mol Biol

ATP causes neurogenic bronchoconstriction in the dog

Drug Dev Res

Lung mechanics during induced bronchoconstriction

J Appl Physiol

Evolving concepts on the value of adenosine hyperresponsiveness in asthma and chronic obstructive pulmonary disease

Thorax

Indirect bronchial hyperresponsiveness in asthma: mechanisms, pharmacology and implications for clinical research

Eur Respir J

Clinical Investigations ASTHMA
Effects of Aerosolized Adenosine 5′-Triphosphate vs Adenosine 5′-Monophosphate on Dyspnea and Airway Caliber in Healthy Nonsmokers and Patients With Asthma