Asthma and lower airway disease
Peripheral lung function in patients with stable and unstable asthma

https://doi.org/10.1016/j.jaci.2013.01.054Get rights and content

Background

Exacerbations of asthma are thought to be caused by airflow obstruction resulting from airway inflammation, bronchospasm, and mucus plugging. Histologic evidence suggests the small airways, including acinar air spaces, are involved; however, this has not been corroborated in vivo by measurements of peripheral small-airway function.

Objective

We sought to determine whether asthma severity is linked to small-airway function, particularly in patients with acute severe asthma.

Methods

Eighteen subjects admitted for an asthma exacerbation underwent lung function testing, including measures of acinar ventilation heterogeneity (Sacin) and conductive ventilation heterogeneity (Scond) using the multiple-breath nitrogen washout. Treatment requirement was defined according to Global Initiative for Asthma scores. Data were compared with those obtained in 19 patients with stable asthma.

Results

For the asthma exacerbation group, the median FEV1 was 59% of predicted value (95% CI, 45% to 75% of predicted value), the median Scond value was 185% of predicted value (95% CI, 119% to 245% of predicted value), and the median Sacin value was 225% of predicted value (95% CI, 143% to 392% of predicted value). FEV1 (percent predicted) was correlated with Sacin (percent predicted) values (Spearman rho = −0.67, P = .006) but not with Scond (percent predicted) values (P > .1). The Global Initiative for Asthma score was significantly related to Sacin (percent predicted) (Spearman rho = 0.59, P = .016) but not to Scond (percent predicted) values (P > .1). The unstable group was characterized by considerably lower forced vital capacity (P < .001) and higher Scond (P = .001) values than the unstable group. In a subgroup of 11 unstable patients who could be reviewed after 4 weeks, FEV1, forced vital capacity, Sacin, and Scond values showed marked improvements.

Conclusion

Our findings suggest that unstable asthma is characterized by a combined abnormality in the acinar and conductive lung zones, both of which are partly reversible. Functional abnormality in the acinar lung zone in particular showed a direct correlation with airflow obstruction and treatment requirement in patients with acute severe asthma.

Section snippets

Subject selection: Asthma exacerbation group

The study was approved by the Alfred Hospital Ethics Committee. Consecutive patients with a severe exacerbation of asthma were recruited on admission to the emergency department at the Alfred Hospital, Melbourne, Australia. Patients were included if their admission peak flow readings were less than 50% of their previously obtained personal best value and did not reach 80% or more of their personal best value after bronchodilator and corticosteroid treatment. Inclusion required a hospital length

Results

Thirty-seven asthmatic patients were studied, including 18 patients admitted acutely to the hospital with an exacerbation of asthma and 19 subjects with stable asthma. Demographics and pulmonary function data are shown in Table I. Even though the asthma exacerbation group had a peak expiratory flow of less than 50% of their personal best value at admission, there was some degree of recovery by the time the patients were tested in the laboratory (within 48 hours). The median peak expiratory flow

Discussion

The most important finding of the present study is the association of FEV1 with Sacin values but not with Scond values within cohorts of patients with an exacerbation of asthma and stable asthma. These data confirm our hypothesis that the function of the acinus is an important determinant of FEV1 in asthmatic patients. In the patients with an asthma exacerbation, there was also an association between Sacin values and GINA step scores. There was no association between Scond values and FEV1 or

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      Citation Excerpt :

      We recognise that a quality check of our approach to attain an optimal phase 3 slope in the MBNW test27 is key to the validity of our measurements, which we have carefully ensured in the present study. The finding that some Sacin values were in the normal range does not contrast with the presence of airway dysfunction in clinical SAD group 1, since most previous studies21,28–34 on ventilation heterogeneity in adult asthma show a variable contribution of conducting versus acinar lung regions to treatment response, and consistency in the reversibility towards normal values after exacerbations.28 Specifically, the persistent disturbance of ventilation in conducting airways (Scond) appears to be related to airway remodelling, exacerbations, and hyperresponsiveness, whereas the reversible disturbance in acinar airway ventilation (Sacin) mainly reflects asthma severity.35

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    Support for this study was provided by the Cooperative Research Centre for Asthma and Airways and the National Health and Medical Research Council, Australia.

    Disclosure of potential conflict of interest: B. R. Thompson, M. J. Ellis, V. J. Kelly, R. E. O'Hehir, and S. Verbanck have received grants from the National Health and Medical Research Council and the Cooperative Research Centre for Asthma and Airways. J. A. Douglass has received grants from the National Health and Medical Research Council and the Cooperative Research Centre for Asthma and Airways; is on an advisory board for Novartis; has received payment for lectures from AstraZeneca, GlaxoSmithKline, and Novartis; and has received royalties from Health Press Limited. G. G. King has received grants from the National Health and Medical Research Council, GlaxoSmithKline, Boehringer Ingelheim, Pharmaxis, and the Asthma Foundation; has received travel support from GlaxoSmithKline, Novartis, AstraZeneca, Boehringer Ingelheim, and Pfizer; has received subject payments for clinical trials from Pharmaxis; and is part of a consultancy agreement between GlaxoSmithKline, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, and the Woolcock Institute of Medical Research, and his research group receives an unrestricted allocation as part of the monies received from the consultancy agreements.

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