Area under flow-volume loop may predict severe exacerbation in COPD patients with high grade of dyspnea

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Highlights

  • AreaFE% was found to be more sensitive parameter than conventional spirometric parameters in the diagnosis of hyperinflation.

  • Hyperinflation is the main underlying mechanism of a COPD exacerbation.

  • Low AreaFE% value is an independent risk factor in addition to a high CAT score in predicting future severe exacerbation.

  • AreaFE% has an excellent discriminative ability in predicting future severe exacerbation.

Abstract

Objective

Exacerbations in patients with COPD may still be unpredictable, although the general risk factors have been well defined. We aimed to determine the role of a novel parameter, area under flow-volume loop, in predicting severe exacerbations.

Methods

In this single-centre retrospective cohort study, 81 COPD patients over 40 years of age with high grade of dyspnea (having a CAT score of ≥10) and a history of ≥1 moderate exacerbation in the previous year were included. Area under flow-volume curve (AreaFE%) was obtained from pulmonary function test graph and calculated from Matlab programme. Univariate and multivariate logistic regression analyses were performed to determine independent risk factors of the severe exacerbation.

Results

Patients with severe exacerbation (n = 70, 86.4 %) were older. They had lower FEV1%, FVC%, 6MWD, AreaFE% and higher CAT score than patients without exacerbation. After performing multivariate analysis, high CAT score and low AreaFE% value were found to be independent risk factors for severe exacerbation (OR: 1.12, 95 % CI: 1.065–1.724; p = 0.01 and OR: 1.18, 95 % CI: 0.732−0.974; p = 0.02).

Conclusions

We found that a low AreaFE% value was an independent risk factor in addition to a high CAT score and these both have an excellent discriminative ability in predicting the risk of severe exacerbation

Introduction

Exacerbation is the major concern in patients with chronic obstructive lung disease (COPD) since it accelerates the decline of lung function, worsens pulmonary symptoms and increases the risk of mortality [[1], [2], [3]]. Having an exacerbation in the previous year and a high grade of dyspnea were determined as the strongest predictors of future exacerbation (OR: 4.30, OR: 1.83; respectively) [4]. Additionally, COPD Assessment Test (CAT) score [5], questioning the respiratory symptoms; BODE index [6], a composite score consisting of modified medical research council (mMRC) score, six minute walking distance (6MWD), forced expiratoy volume in the first second (FEV1%) and body mass index (BMI) and some peripheral blood biomarkers such as eosinophil count [[7], [8], [9]] and neutrophil/lymphocyte ratio (NLR) [10] were defined as other predictors. However, none of these are adequate alone, there is an ongoing need to investigate more accurate parameter in predicting the future exacerbation.

Hyperinflation, defined as the presence of air trapping, is the main underlying mechanism of an exacerbation in many patients and contributes to disease severity [11]. It is the ratio of residual volume (RV) to total lung capacity (TLC) measured by using body plethysmography. Korean Obstructive Lung Disease (KOLD) cohort study revealed that it predicts future exacerbations in COPD patients [12]. Despite the good performance of body plethysmography, it is not commonly used in many outpatient clinic, and it is difficult to meet the acceptability criteria of forced expiratory maneuver during this procedure for elderly patients with high grade of dyspnea. Instead, a novel spirometric parameter, area under flow-volume loop (AreaFE%) derived from the standard spirometric flow volume loop (FVL); which is the ratio of the actual area under FVL to the reference area under FVL can be used in clinical practice. Nilakash et al. demonstrated that AreaFE% is superior to conventional spirometric parameters in estimating hyperinflation (Diagnostic accuracy for AreaFE% = 81 % vs FEV1% = 72 % vs FEV1/FVC = 57 %) [13]. Additionally, this novel parameter was found to be useful by the present authors in predicting hyperinflation by determining presence of emphysema in patients with COPD-Bronchiectasis overlap sydrome (AUC for AreaFE% = 0.82 vs FEV1 = 0.63 vs FEV1/FVC = 0.59) [14]. Despite these reported superiorities, the relationship between AreaFE% and the risk of future exacerbation has not been well established. In line with that, we aimed to indicate whether the novel parameter ‘AreaFE%’ is helpful in predicting severe COPD exacerbation in patients with high grade of dyspnea.

Section snippets

Study design and setting

We performed a retrospective cohort study conducted at University of Health Science, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul in patients seen at the respiratory outpatient clinic. The respiratory clinic at University of Health Science, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul is a tertiary referral center for pulmonary diseases, managing adult patients. Our study was conducted in line with the Declaration

Results

A total of 81 patients were included in the study. Of which, 70 patients (86.4 %) did not have a severe exacerbation, while 11 patients (13.6 %) had a severe exacerbation in the following year. Mean age was 60.9 ± 9.1 years and 73 patients (90.1 %) were male. Univariate analyses revealed that there was no significant difference between groups in terms of gender, smoking status, BMI, biomass exposure, having pneumococcal and influenza vaccine, FEV1/FVC, eosinophil count, NLR, bronchodilator

Discussion

In our study, we investigated the role of ‘AreaFE%’ in predicting severe exacerbation in COPD patients with high grade of dyspnea. Our data showed that lower AreaFE% value and higher CAT score were independently associated with the risk of a severe exacerbation. They have excellent discriminative ability and might be clinically useful for determining and closely monitoring the patients prone to severe exacerbation.

Demographic characteristics take an important place in determining the risk of

Conclusions

Low AreaFE% values and high CAT scores were determined as independent factors in predicting severe exacerbation in COPD patients with high grade of dyspnea. Our finding was limited to COPD patients without a severe exacerbation in the preceding year

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contribution statement

Celal Satıcı conceived and designed the study; Burcu Arpinar Yigitbas and Celal Satıcı performed the patient management and collection of the data; Mustafa Asim Demirkol analyzed and interpreted the data; A.Filiz Kosar and Burcu Arpinar Yigitbas contributed reagents, materials, analysis tools or data; Celal Satıcı, Mustafa Asim Demirkol, A.Filiz Kosar and Burcu Arpinar Yigitbas wrote the paper.

The manuscript has been read and approved by all the authors, that the requirements for authorship as

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (34)

  • T. Motegi et al.

    A comparison of three multidimensional indices of COPD severity as predictors of future exacerbations

    Int. J. COPD

    (2013)
  • C. Casanova et al.

    Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD

    Eur. Respir. J.

    (2017)
  • S. Vedel-Krogh et al.

    Blood eosinophils and exacerbations in chronic obstructive pulmonary disease: the Copenhagen general population study

    Am. J. Respir. Crit. Care Med.

    (2016)
  • J.H. Yun et al.

    Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

    J. Allergy Clin. Immunol.

    (2018)
  • P. Paliogiannis et al.

    Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives

    Eur. Respir. Rev.

    (2018)
  • Y.W. Kim et al.

    Resting hyperinflation and emphysema on the clinical course of COPD

    Sci. Rep.

    (2019)
  • N. Das et al.

    Area under the forced expiratory flow-volume loop in spirometry indicates severe hyperinflation in COPD patients

    Int J COPD

    (2019)
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