Inflammation and airway function in the lung periphery of patients with stable asthma

doi:10.1016/j.jaci.2009.10.053

Journal of Allergy and Clinical Immunology

Volume 125, Issue 3, March 2010, Pages 611-616

https://doi.org/10.1016/j.jaci.2009.10.053 Get rights and content

Background

An important role for exhaled nitric oxide (NO) measurement could be in the distinction between proximal and peripheral lung contributions to inflammation, with a particular interest for the alveolar lung zone and its implication on airway function.

Objective

We aimed to isolate the acinar lung zone contribution to both inflammation and airway function to seek a relationship between them.

Methods

In 30 patients with asthma with an asthma control test score exceeding 20, indices of conductive and acinar ventilation heterogeneity (Scond, Sacin) were obtained from a multiple breath washout. NO production in the conductive airways (J'aw_NO), alveolar NO concentration (CA_NO), and the standard exhaled NO at 50 mL/s (FENO₅₀) were obtained from exhaled NO.

Results

Scond was consistently abnormal in all patients with stable asthma, but without any correlation to inflammation abnormality in that compartment (J'aw_NO). Sacin was particularly abnormal in the asthma subgroup receiving >500 μg budesonide equivalent, and a correlation was found between Sacin and CA_NO (r = 0.61; P = .015); in this subgroup, a weak association was found between Scond and J'aw_NO or FENO₅₀ (r = 0.50; P = .059 for both).

Conclusion

The persistent functional abnormality of small conductive airways in patients with stable asthma is largely independent of inflammation as measured by exhaled NO. In the alveolar compartment, a functional correlate of alveolar NO was found in a subgroup of patients with stable asthma on moderate-to-high maintenance doses of inhaled steroids. These patients in particular could benefit from novel therapies specifically aimed at improving airway functionality at the level of the acinar entrance and beyond.

Section snippets

Methods

The protocol was approved by the local ethics committee (#B14320071296), and informed consent was obtained from all participating subjects. A set of measurements was performed in patients with asthma and in a healthy control group. Measurements in the asthma group were done postdilatation with 400 μg salbutamol, thereby minimizing variable smooth muscle contraction, to assess any residual structure-function abnormality in these patients with stable asthma. Of all measured parameters, normal

Results

All patients had clinically diagnosed asthma and documented reversibility (n = 30; 14 women, 16 men; 44.5 ± 15.2 [SD] years; 172 ± 10 [SD] cm). All patients were atopic and had been treated by inhaled corticosteroids in combination with long-acting β₂ mimetics for at least 5 years. None of the patients were treated with oral corticosteroids. All patients with asthma were clinically stable, and their reported ACT score ranged from 20 to 25.²⁶ Two asthma subgroups were distinguished according to

Discussion

In this study we have first identified the conductive airways contribution to ventilation heterogeneity which was accompanied by, but largely unrelated to, an abnormally high airway NO production as measured from exhaled NO in patients with otherwise stable asthma. Possibly the conductive ventilation heterogeneity observed here was at least in part the functional consequence of a nonsteroid-responsive structural change associated with airway remodeling. If such remodeling is present early in

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View all citing articles on Scopus

: Supported by the Fund for Scientific Research—Flanders and the NO Microgravity Application Project of the European Space Agency.

: Disclosure of potential conflict of interest: S. Verbanck has received research support from the Fund for Scientific Research and the European Space Agency. The rest of the authors have declared that they have no conflict of interest.

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Asthma and lower airway diseaseInflammation and airway function in the lung periphery of patients with stable asthma

Background

Objective

Methods

Results

Conclusion

Section snippets

Methods

Results

Discussion

Chest

Chest

J Allergy Clin Immunol

Allergol Int

J Allergy Clin Immunol

Chest

Respir Med

Basal and induced NO formation in the pharyngo-oral tract influences estimates of alveolar NO levels

J Appl Physiol

Effect of airways constriction on exhaled nitric oxide

J Appl Physiol

ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005

Am J Respir Crit Care Med

Reference ranges for exhaled nitric oxide derived from a random community survey of adults

Am J Respir Crit Care Med

The effects of age on exhaled breath nitric oxide levels

Lung

Extended NO analysis in a healthy subgroup of a random sample from a Swedish population

Clin Physiol Funct Imaging

The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial

Am J Respir Crit Care Med

NO more dogma: nitric oxide marker in asthma

Am J Respir Crit Care Med

Exhaled nitric oxide: still alive, not laid to rest

Am J Respir Crit Care Med

Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients

Eur Respir J

Alveolar nitric oxide versus measures of peripheral airway dysfunction in severe asthma

Eur Respir J

Asthma and lower airway disease
Inflammation and airway function in the lung periphery of patients with stable asthma