0
Point and Counterpoint |

Point: Is an Increase in FEV1 and/or FVC ≥ 12% of Control and ≥ 200 mL the Best Way to Assess Positive Bronchodilator Response? YesFEV1 for Bronchodilator Response? Yes FREE TO VIEW

Riccardo Pellegrino, MD; Vito Brusasco, MD
Author and Funding Information

From the Allergologia e Fisiopatologia Respiratoria (Dr Pellegrino) and Dipartimento di Medicina Interna e Specialità Mediche (Dr Brusasco), Scuola di Scienze Mediche e Farmaceutiche, Università di Genova.

CORRESPONDENCE TO: Riccardo Pellegrino, MD, Allergologia and Fisiopatologia Respiratoria, ASO S Croce e Carle, 12100 Cuneo, Italy; e-mail: pellegrino.r@ospedale.cuneo.it


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(3):536-537. doi:10.1378/chest.14-0810
Text Size: A A A
Published online

According to the American Thoracic Society/European Respiratory Society document on lung function testing, FEV1 and FVC are the key parameters to assess bronchoreversibility in obstructive lung diseases because spirometry is easy to perform in any setting, repeatable and reproducible, and, thus, suitable to assess either intraday or long-term changes in lung function.1 The acute response to bronchodilators is relatively easy to interpret when changes in FEV1 or FVC exceed the thresholds of their natural intraday variability (ie, 12% of baseline and 200 mL), thus, unequivocally indicating bronchodilation. Although the bronchodilator response does not allow a distinction between bronchial asthma and COPD,2,3 large responses can be taken as strongly suggestive of the former.4 Therefore, we believe that changes in FEV1 or FVC still represent the most suitable first-line method to assess bronchodilator response in clinical practice.

Nevertheless, some physiologic mechanisms need to be considered, particularly for the interpretation of borderline or negative responses. Bronchodilators relax airway smooth muscle, thus increasing airway caliber. However, the relationship between increase in airway diameter and FEV1 is not linear for at least three major reasons. First, airway wall stiffness is reduced when airway smooth muscle is relaxed. Being that airway diameter and collapsibility are the major determinants of maximal flow,5 the net effect of a bronchodilator on airway caliber is consistently underestimated by the increase in FEV1. Second, the deep inspiration preceding the forced expiratory maneuver has variable effects on airway caliber that depend on the mechanical properties of the airways and lung parenchyma.6 It has been shown that bronchodilators have less effect on forced expiratory flow measured after deep inspiration than before.7 This could be because inhaled bronchodilators reduce airways more than parenchymal hysteresis or because they are preferentially distributed to lung regions with shorter time constants, which empty earlier during forced expiration, thus contributing to the increase in flow more after a partial than a maximal forced expiratory maneuver.8 These artifacts may partly explain why some patients feel better after bronchodilators despite no changes in FEV1 or FVC, which is possibly due to tidal breathing being shifted to lower lung volumes where the work of breathing is reduced.9 Third, during a forced expiratory maneuver, alveolar pressure increases depending on expiratory effort, absolute lung volume, and airflow resistance. As a consequence, part of the gas is compressed and does not contribute to the FEV1. One study showed such a volume decrease after treatment with salbutamol in COPD because of a decrease in lung resistance and lung hyperinflation, with the latter accounting for about 23% of the increase in FEV1.10 Thus, changes in FEV1 may even overestimate the effect of bronchodilators on airway caliber, depending on absolute lung volume. It should be noted that the measurement of FVC is also influenced by the reduction in airway wall stiffness and volume history but not by gas compression.11,12

Because symptoms are more likely related to tidal breathing than forced expiratory maneuver, it has been suggested that measurements of airway resistance provide a better estimate of the effects of bronchodilators than spirometry. Yet it must be acknowledged that measurement of airway resistance is not widely accessible in clinical practice. In addition, the measurement is not as sensitive to changes in airway caliber as expected for several reasons.13 First, important increments of peripheral airway caliber may go undetected because of their small contribution to total airways resistance. Second, the relationship between airway caliber and resistance is not linear, which is a reason why the decrease in resistance after a bronchodilator is larger in advanced than in mild airflow obstruction. Third, the correction of resistance for lung volume may not apply to disease conditions if airway-to-parenchyma interdependence is lost. Fourth, expiratory flow limitation over the tidal volume range may affect measurements of airway resistance. New, important windows may be opened in the assessment of bronchodilator responses by the use of the forced oscillation technique, which allows for measuring resistance as a function of lung volume. By using this method, we observed different effects of albuterol on airway distensibility between subjects with COPD with prevalent airway or parenchymal disease.14 In another study, it was reported that the SD of resistance was the parameter that changed the most in children with asthma after inhaling albuterol, suggesting that temporal variability of airway function may be much more informative about the effect of bronchodilators than one-shot measurements like spirometry.15 Notwithstanding, we must wait for further clinical validation and application of these tests in clinical practice.

In summary, any physiologic test used to assess bronchoreversibility in clinical practice carries advantages and limitations because the lung is a complex organ and its function cannot be embodied by a single test. Spirometry has been used for decades to this aim because it is simple, well standardized, and available in almost every setting and may carry sufficient information if changes exceed the threshold of natural variability. Software incorporating the measurement of inspiratory capacity may help to evaluate the decrease in lung volume within the tidal breathing range. When the test yields ambiguous results, lung function examined over time will be of great help to clarify the doubts. For all these reasons, we believe that spirometry is still preferable to any other tests, at least for clinical applications. In theory, airflow resistance would better reflect lung mechanics during tidal breathing, which is unquestionably more relevant to daily life than forced expiratory maneuvers, but measurements are less reproducible and technically more demanding and results quite often difficult to interpret. Even though we support spirometry as a key test to evaluate bronchoreversibility, we believe that compression-free spirometry and measurements free of volume history effects that explore temporal and volume domains of airway mechanics will be of great help in the future to best assess lung function under clinical and research conditions.

Abbreviations

ATS/ERS

American Thoracic Society/European Respiratory Society

CL

confidence limit

SS

statistically significant

Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948-968. [CrossRef] [PubMed]
 
Eliasson O, Degraff AC Jr. The use of criteria for reversibility and obstruction to define patient groups for bronchodilator trials. Influence of clinical diagnosis, spirometric, and anthropometric variables. Am Rev Respir Dis. 1985;132(4):858-864. [PubMed]
 
Anthonisen NR, Wright EC. Bronchodilator response in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1986;133(5):814-819. [PubMed]
 
National Collaborating Centre for Chronic Conditions. Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax. 2004;59(suppl 1):1-232.
 
Hyatt RE. Forced expiration.. In:Macklem PT, Mead J., eds. Handbook of Physiology. The Respiratory System. Mechanics of Breathing.Vol 3. Bethesda, MD: American Physiological Society; 1986:295-314.
 
Froeb HF, Mead J. Relative hysteresis of the dead space and lung in vivo. J Appl Physiol. 1968;25(3):244-248. [PubMed]
 
Wang YT, Thompson LM, Ingenito EP, Ingram RH Jr. Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis. J Appl Physiol (1985). 1990;68(1):363-368. [PubMed]
 
Pedersen OF, Butler JP. Expiratory flow limitation. Compr Physiol. 2011;1(4):1861-1882. [PubMed]
 
Pellegrino R, Rodarte JR, Brusasco V. Assessing the reversibility of airway obstruction. Chest. 1998;114(6):1607-1612. [CrossRef] [PubMed]
 
Sharafkhaneh A, Babb TG, Officer TM, Hanania NA, Sharafkhaneh H, Boriek AM. The confounding effects of thoracic gas compression on measurement of acute bronchodilator response. Am J Respir Crit Care Med. 2007;175(4):330-335. [CrossRef] [PubMed]
 
Pellegrino R, Violante B, Selleri R, Brusasco V. Changes in residual volume during induced bronchoconstriction in healthy and asthmatic subjects. Am J Respir Crit Care Med. 1994;150(2):363-368. [CrossRef] [PubMed]
 
Brusasco V, Pellegrino R, Rodarte JR. Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories. Eur Respir J. 1997;10(6):1316-1320. [CrossRef] [PubMed]
 
Ingram RH Jr, Pedley TJ. Pressure-flow relationships in the lungs.. In:Macklem PT, Mead J., eds. Handbook of Physiology. The Respiratory System. Mechanics of Breathing.Vol 3. Bethesda, MD: American Physiological Society; 1986:277-293.
 
Baldi S, Dellacà R, Govoni L, et al. Airway distensibility and volume recruitment with lung inflation in COPD. J Appl Physiol (1985). 2010;109(4):1019-1026. [CrossRef] [PubMed]
 
Lall CA, Cheng N, Hernandez P, et al. Airway resistance variability and response to bronchodilator in children with asthma. Eur Respir J. 2007;30(2):260-268. [CrossRef] [PubMed]
 

Figures

Tables

References

Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948-968. [CrossRef] [PubMed]
 
Eliasson O, Degraff AC Jr. The use of criteria for reversibility and obstruction to define patient groups for bronchodilator trials. Influence of clinical diagnosis, spirometric, and anthropometric variables. Am Rev Respir Dis. 1985;132(4):858-864. [PubMed]
 
Anthonisen NR, Wright EC. Bronchodilator response in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1986;133(5):814-819. [PubMed]
 
National Collaborating Centre for Chronic Conditions. Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax. 2004;59(suppl 1):1-232.
 
Hyatt RE. Forced expiration.. In:Macklem PT, Mead J., eds. Handbook of Physiology. The Respiratory System. Mechanics of Breathing.Vol 3. Bethesda, MD: American Physiological Society; 1986:295-314.
 
Froeb HF, Mead J. Relative hysteresis of the dead space and lung in vivo. J Appl Physiol. 1968;25(3):244-248. [PubMed]
 
Wang YT, Thompson LM, Ingenito EP, Ingram RH Jr. Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis. J Appl Physiol (1985). 1990;68(1):363-368. [PubMed]
 
Pedersen OF, Butler JP. Expiratory flow limitation. Compr Physiol. 2011;1(4):1861-1882. [PubMed]
 
Pellegrino R, Rodarte JR, Brusasco V. Assessing the reversibility of airway obstruction. Chest. 1998;114(6):1607-1612. [CrossRef] [PubMed]
 
Sharafkhaneh A, Babb TG, Officer TM, Hanania NA, Sharafkhaneh H, Boriek AM. The confounding effects of thoracic gas compression on measurement of acute bronchodilator response. Am J Respir Crit Care Med. 2007;175(4):330-335. [CrossRef] [PubMed]
 
Pellegrino R, Violante B, Selleri R, Brusasco V. Changes in residual volume during induced bronchoconstriction in healthy and asthmatic subjects. Am J Respir Crit Care Med. 1994;150(2):363-368. [CrossRef] [PubMed]
 
Brusasco V, Pellegrino R, Rodarte JR. Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories. Eur Respir J. 1997;10(6):1316-1320. [CrossRef] [PubMed]
 
Ingram RH Jr, Pedley TJ. Pressure-flow relationships in the lungs.. In:Macklem PT, Mead J., eds. Handbook of Physiology. The Respiratory System. Mechanics of Breathing.Vol 3. Bethesda, MD: American Physiological Society; 1986:277-293.
 
Baldi S, Dellacà R, Govoni L, et al. Airway distensibility and volume recruitment with lung inflation in COPD. J Appl Physiol (1985). 2010;109(4):1019-1026. [CrossRef] [PubMed]
 
Lall CA, Cheng N, Hernandez P, et al. Airway resistance variability and response to bronchodilator in children with asthma. Eur Respir J. 2007;30(2):260-268. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
COPD: obstructed lungs. Nurs N Z 2016;22(5):20-4.
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543