Expert Review of Respiratory Medicine

ISSN: 1747-6348 (Print) 1747-6356 (Online) Journal homepage: https://www.tandfonline.com/loi/ierx20

Advances in spirometry testing for lung function

analysis

Agnaldo José Lopes

To cite this article: Agnaldo José Lopes (2019): Advances in spirometry testing for lung function
analysis, Expert Review of Respiratory Medicine, DOI: 10.1080/17476348.2019.1607301

To link to this article: https://doi.org/10.1080/17476348.2019.1607301

Accepted author version posted online: 12

Apr 2019.

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 Publisher: Taylor & Francis

Journal: Expert Review of Respiratory Medicine

DOI: 10.1080/17476348.2019.1607301
Advances in spirometry testing for lung function analysis

Agnaldo José Lopes1,2

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Post-graduate Program in Medical Sciences, State University of Rio de Janeiro, Rio de

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Janeiro, Brazil.
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Rehabilitation Sciences Master’s Program, Augusto Motta University Center, Rio de

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Janeiro, Brazil. an
CONTACT: Agnaldo José Lopes. Rehabilitation Sciences Master’s Program, Augusto
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Motta University Center, Praça das Nações, 34, Bonsucesso, 21041-010, Rio de Janeiro,

Brazil. Phone: +55 21 21 2576 2030. Email: agnaldolopes.uerj@gmail.com

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 ABSTRACT

Introduction: Spirometry, the most common lung function test, is used to evaluate

individuals with respiratory complaints or known respiratory disease. However, its

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underutilization and the misinterpretation of its parameters are causes for concern.

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Areas covered: This review describes new spirometry-derived metrics, new reference

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equations, recent recommendations for presentation of results, recent spirometry-based

prevalence studies, and technological advances in spirometry equipment.

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Expert Opinion: The underutilization of spirometry can be overcome by increasing
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access to portable, hand-held, and user-friendly spirometers, together with strategies

that increase awareness of the importance of spirometry. New metrics derived from
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spirometry, together with traditional spirometric criteria, can identify individuals with

structural lung disease and respiratory morbidity. Some problems with the reference
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equations were solved by the Global Lung Function Initiative (GLI), which covers a
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wider age range and more ethnic groups and provides limits of normality using the z-

score. Despite these advantages, the GLI equations lack data from large populations
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(especially those from Africa, South Asia, and Latin America) and greater

representation of older people. Another disadvantage attributed to the GLI is the lack of

predicted values for peak expiratory flow and other airflows, limiting the interpretation

of the maximal expiratory flow-volume curve.

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 Keywords: Spirometry; pulmonary function; reference equations; asthma; chronic

obstructive pulmonary disease; education; new technologies

Article Highlights

• Increased use of spirometry may result in an increased proportion of patients

diagnosed early from a functional point of view and, possibly, in better

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management of airway disease during follow-up.

• New metrics derived from maximal expiratory volume-time and maximal

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expiratory flow-volume curves are associated with structural lung disease,

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dyspnea, and respiratory quality of life in computed tomography and may be

useful for individuals with borderline or mild lung disease according to

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traditional spirometric criteria.

• There has been much enthusiasm for adopting Global Lung Function Initiative
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(GLI) equations because they are applicable to a wider age range and more
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ethnic groups and eliminate problems related to shifting between equations

during growth.
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• A graph showing the differences between test results and predicted values in

standard deviation units (z-score) may help with understanding abnormalities in

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lung function.
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• In spirometry reports, attention should be given to the limited number of

parameters and presenting the lower limit of normal next to the measured value

can improve the interpretive precision of the test.

• The international data repository of the GLI allows the development and

ongoing evaluation of reference values.

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 • In addition to overdiagnosis in the elderly, Global Initiative for Chronic

Obstructive Lung Disease criteria may underestimate the diagnosis of chronic

obstructive pulmonary disease (COPD) in younger patients.

• Spirometry is not sufficiently sensitive to detect structural changes in all patients

at risk, and therefore, it should be complemented with imaging tests and other

functional tests.

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• Spirometry performed in the workplace should be part of a comprehensive

respiratory health program.

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• Spirometric parameters appear to be more important than fractional exhaled

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nitric oxide measurements for predicting the outcomes of asthma.

• In addition to spirometric parameters, the diagnosis of asthma-COPD overlap

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should consider environmental exposure, especially in low- and middle-income
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countries.
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 1. Introduction

Organ volume measurements date from the second century, when Claudius Galenus

measured variations in bladder volume before and after the bladder was inflated by a

boy. Pulmonary function measurement was later developed by physiologists, including

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Giovani Borelli (1608-1679), Humphry Davy (1778-1829), and Nestor Grehant (1838-

1910), whose sketches of their gasometers are still available. The first known

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spirometer was developed by the English physician John Hutchinson in 1846 [1].

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Spirometry is the most commonly performed pulmonary function test (PFT) in

pulmonary practice because of its simplicity and reproducibility. It is widely used to

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diagnose and evaluate the severity of clinical conditions and to assess and quantify the

effects of pulmonary disease treatments [2]. Despite its clinical relevance, spirometry is
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underused due to a lack of awareness of its importance, limited access to the test [3,4],

and inappropriate techniques [5,6] and interpretations [7,8]. Several medical societies
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have published guidelines for standardizing the test methodology and improving data
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interpretation [9–11].

There have been significant technological advancements in spirometers in recent

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decades, especially those related to portable devices. Furthermore, new indices and

ways of analyzing test results have been proposed, which may be useful for individuals
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with borderline or mild lung disease based on traditional spirometric criteria [12,13]. A

more recent cause for concern is the presentation of results [14]. Numerous variables

can be tested, and large amounts of data can be obtained; however, not all results are

equally relevant. Moreover, excessive data may lead to an incomplete understanding of

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 the analysis. This problem can be avoided by using a more concise report format and

presenting data in a standard format.

This narrative review addresses the technical aspects that should guide the

execution of spirometry and provides new insights. This review also describes

population-based studies that stress the importance of this method, proposals for using a

standard report model, and new reference equations for interpreting the results, with an

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emphasis on the multinational population study conducted by the Global Lung Function

Initiative (GLI) Network. Recent technological advancements in spirometry equipment

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are also presented.

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2. Spirometric parameters and their importance
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Spirometry requires the understanding and collaboration of the patient, accurate

equipment, and the application of standardized techniques by specially trained

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personnel. According to the ATS/ERS task force, the main spirometry parameters are

vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first
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second (FEV1), and the relationship between these parameters (FEV1/VC or

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FEV1/FVC) [11]. In addition to airflow and volume, analysis of the shape of the

volume-time and volume-flow curves may provide important information (Figure 1).
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The maximal expiratory flow-volume (MEFV) curve shows that the flow is maximal at

the beginning of expiration and decreases as the lung volume approaches the residual
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volume (RV). Flow volumes at the beginning of expiration correspond to the effort-

dependent portion of the curve because they can increase with greater patient effort. The

maximum flow volumes after expiration of the first 30% of the FVC occur with modest

expiratory effort and represent the effort-independent portion of the curve [10,11].

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 Flow volumes generated from the middle of the MEVT curve, including the

forced expiratory flow in the middle half of the FVC (FEF25-75%), are largely effort-

independent but rely heavily on lung volume and airway size [15]. Thus, the normal

range for these flow volumes is much larger than those for effort-dependent measures

such as FEV1 and peak expiratory flow (PEF). This disadvantage of intermediate and

end flow volumes is partially offset by their significant changes in disease states,

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causing them to be abnormal in isolation in the early stages of an obstructive defect and

consequently indicating small-airway disorder (SAD) [13].

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The forced expiratory volume in the third second/FVC (FEV3/FVC) ratio is

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recommended by some authors as a routine spirometric measure to diagnose airflow

limitation (AFL) [13,16]. Bhattarai et al. [17] showed that more than 10% of subjects
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with a normal FEV1/FVC ratio presented an abnormal FEV3/FVC ratio, and this

parameter was more accurate than FEF25-75% for diagnosing SAD. Piorunek et al. [13]
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compared the utility of FEV3/FVC and the difference in airway resistance at 5 Hz and
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20 Hz (R5-R20) measured by impulse oscillometry (IOS) in chronic obstructive

pulmonary disease (COPD). R5-R20 was highly sensitive for detecting mild lung
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disease, and FEV3/FVC was highly specific for excluding a SAD diagnosis. Although

spirometry and IOS are complementary for diagnosing SAD [18], the importance of
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FEV3/FVC has not yet been discussed in the guidelines of the American Thoracic

Society (ATS)/European Respiratory Society (ERS) [9,11,14].

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The forced expiratory volume in the sixth second (FEV6) is a convenient

alternative for FVC [19]. Because of the 6-second expiratory maneuver, FEV6

spirometry in the clinic is easier, faster, and safer than FVC measurement [20].

Furthermore, FEV1/FEV6 use simplifies testing procedures and reduces data variability,

improving diagnostic accuracy [16,19], although the cut-off points to define obstructive

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 defects remain controversial. In this respect, Wang et al. [21] demonstrated that an

FEV1/FEV6 ratio <0.72 might be used in primary care as an alternative to an FEV1/FVC

ratio <0.70 as a fixed cut-off point for detecting COPD. FEV6 is useful in some clinical

settings but has been associated with misdiagnoses in older adults. Therefore, in the

elderly, there may be excessive diagnoses of AFL using FEV1/FEV6, indicating that

fixed cut-off values should be used with caution [19].

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In children unable to perform forced maneuvers for 1 second, the forced

expiratory volume in 0.5 seconds (FEV0.5) or the forced expiratory volume in 0.75

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seconds (FEV0.75) can be used as alternatives to FEV1 [10]. More recently, the

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FEV0.75/FVC ratio was useful to evaluate wheezing management in preschool children

because there is an association between wheezing and reduced FEV0.75/FVC [22].

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Chawes [23] used biomarkers of disease activity and lung function to assess the

subsequent onset of asthma and allergy during the first 7 years of life and found that
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reduced FEV0.5 was significantly associated with elevated C-reactive protein and other
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inflammatory markers, suggesting the occurrence of low-grade systemic inflammation

from early childhood.

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3. Recommendations for spirometry interpretation

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3.1. Strategies for interpreting the test

According to the ATS/ERS task force, the FEV1/VC ratio is the main parameter
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used to define obstructive defects [11]. Both FEV1 and VC are decreased in restrictive

defects, leading to a normal FEV1/VC ratio. Because FEF25-75% and other instantaneous

airflow measurements are not accurate for diagnosing AFL in cases in which the

FEV1/VC ratios are borderline [15,24], clinical and radiological correlations are helpful

in these cases by indicating the presence or absence of an obstructive defect. It is

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 important to evaluate radiographs or computed tomography (CT) scans to aid in

interpretation [25].

A fixed value of 80% to predict the lower limit of normal (LLN) has been used

in children, although this may cause significant errors in interpreting spirometric

parameters in adults and the elderly [26]. Using a fixed value of 0.70 of the FEV1/FVC

ratio as the lower limit may result in overdiagnosis of COPD in asymptomatic older

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adults who have never smoked [27]. Thus, clinical decisions based on fixed values

should be evaluated with caution considering the age group [9]. FEV1/FVC values are

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independent of ethnicity, and therefore the LLN is a useful indication of AFL, even

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when ethnicity is uncertain [14]. The difference between FVC and slow VC (VC–FVC)

is associated with AFL in patients with obstructive defects [11]. Although this
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measurement is simple and easily obtained, Martinez et al. [28] demonstrated that it was

weakly correlated with dynamic lung hyperinflation assessed by serial measurements of

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inspiratory capacity during the 6-minute walk test in patients with COPD. This result
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suggests that lung volumes evaluated using PFTs at rest provide insufficient information

on ventilatory performance during exercise.

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Traditional spirometric indices for diagnosing obstructive defects do not detect

approximately 50% of individuals with respiratory symptoms or structural lung disease

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confirmed through CT [29]. For earlier AFL diagnosis, the isolated decrease in FEF25-

may help diagnosis mild airway obstruction in symptomatic smokers, despite its
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75%

high variability [11,16]. Bhatt et al. [12] used advanced computational tools combined

with mathematical models to correlate pulmonary disease parameters in CT scans with

AFL metrics based on MEVT (Parameter D) and MEFV (Transition Point and

Transition Distance) curves (Figure 2). All assessed metrics had significant associations

with emphysema, SAD, dyspnea, and quality of life (QoL). Parameter D identified 9.5%

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 of individuals with structural lung disease and was independently associated with all-

cause mortality. To differentiate healthy older adults from those with mild COPD,

Dominelli et al. [30] calculated the slope ratio at 20-80% of the MEFV curve to

quantify its concavity. More recently, Wang et al. [31] used the “angle of collapse” of

the MEFV curve ≤137° to diagnose patients with asthma-COPD overlap (ACO) with

significant emphysema, with sensitivity and specificity of 62.5% and 89.1%,

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respectively.

Restrictive defects are defined by a decrease in total lung capacity (TLC)

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[11,32]. However, a decreased VC value with preserved FEV1/VC in a clinical and

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radiological context suggestive of a restrictive defect should be valued, especially

because methodologies for measuring RV are currently unavailable in many PFT

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laboratories [11,33]. In these situations, the examiner should indicate that reduced VC is

likely due to a restrictive defect [11]. Although VC reduction is usually not

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accompanied by TLC reduction, the opposite is not true, and there is a good correlation
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between normal VC and absence of reduced TLC. Therefore, complementation with the

measurement of TLC is not necessary in the presence of a normal VC value [11].

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Spirometric parameters are used to classify functional defects. The ATS/ERS

recommendation is to use %FEV1 as the basis for this classification [11], although this
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approach uses an arbitrary number of severity categories. Thus, the use of the %

predicted in this way entails a pronounced age-related bias. Quanjer et al. [34] evaluated
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an alternative to grade obstructive defects and thereby overcome biases related to age,

height, and gender. Using a simple classification system, these authors proposed the

LLN for FEV1/(F)VC and z-scores for FEV1 of -2, -2.5, -3 and -4 to delineate severity

levels of AFL.

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 3.2. New recommendations for presenting results

Although previous guidelines provided guidance on reporting spirometry data, there is

considerable variability in the presentation of results. Commercial PFT systems offer

different reports, and some clinical laboratories customize their reports. These

approaches may lead to confusion and make it difficult to compare results from

different laboratories. The ATS recently recognized the need for a standardized

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reporting format for PFTs [14]. The committee emphasizes that simplifying the data

presented in the final report is essential for improving clinicians’ understanding of

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spirometry, which may lead to a strong incentive for its use.

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The ATS recently recommended that only relevant variables be included in the

report because including a large number of variables increased the probability of one
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variable falling below an arbitrary LLN, consequently increasing the chances of a false-

positive result. To avoid excessive data, the predicted values should be omitted because
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they do not help interpret the abnormality; instead, the LLN value should be prioritized.
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Regardless of the reference source or the chosen LLN, examiners should be aware of

uncertainties when interpreting values close to any dichotomous limit [32,35].

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Normal data from several predicted equations may change considerably, and the

use of the predicted percentage leads to an age bias because the variability in spirometry
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tests varies widely during the lifetime. However, age bias can be avoided by using a z-

score specific for sex, age, and height [36]. In this respect, the ATS stresses the
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importance of presenting a z-score, which is the number of standard deviations (SDs)

from the mean or, for regression equations, the number of standardized residuals from

the predicted value (Figure 3). Linear graphs show the z-scores for the normal range,

helping to evaluate the significance of abnormal values because these scores indicate

disease severity relative to the predicted value [32]. In contrast to the predicted

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 percentage, the z-score is free from bias inherent to anthropometric variables and,

consequently, is useful for defining the lower and upper limits of normality. Moreover,

the z-score simplifies the uniform interpretation of test results [36].

The simplified report model proposed by the ATS (Figure 4) does not emphasize

that all obtained curves should be available to improve analysis by clinicians. Height,

weight, sex, and ethnicity should also be included in the report; when evaluating test

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results, age should be recorded in years with an accuracy of at least one decimal place

during periods of rapid growth (preferably as the date of measurement minus the date of

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birth). For any height and sex, a difference of 1 year in age may change the predicted

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value by up to 8.5% in individuals <20 years [37]. The absolute values and predicted

percentages of FVC and FEV1 should be reported. For FEV1/FVC, reporting only the
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absolute value as a decimal fraction (leaving the column for the predicted percentage

blank) has been recommended by the ATS to avoid confusion in interpretation (Figure
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4) [32,35]. In patients with suspected AFL, the vital capacity (VC) and FEV1/VC values
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can also be shown in separate columns [14].

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4. New reference equations for spirometry tests

The differences between reference equations stem from factors including health of the
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individuals selected, sample size, equipment used, quality control, and statistical

method used to calculate the equations [14,38,39]. These differences may significantly
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impact data interpretation, and the results for the same individual may be abnormal

using one equation but normal using another [40]. Anthropometric characteristics are

insufficient to explain differences in lung function between ethnicities; therefore, it is

important to consider factors other than conventional anthropometric measures [40]

(Figure 5). One of the oldest problems with reference equations is the lack of a single

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 reference source for monitoring individuals from infancy to old age [14]. Prediction

equations usually cover a limited age range, leading to inconsistencies as individuals

move from one set of equations used in an age group to another set used in another age

group. Many pediatric equations include only height and omit age because of rapid

growth during childhood, leading to bias in preschoolers and teenagers. An important

barrier to the creation of an equation for all age groups was the limited availability of

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statistical methodologies, although the recent availability of more flexible

methodologies has allowed modeling complex nonlinear relationships across a broad

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age range [39].

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The solution to many of these problems was obtained by the GLI Network,

which shared more than 74,000 medical records from 26 countries from various ethnic
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groups, including Caucasians, African Americans, and Asians [14,39]. Because many

populations were not represented in these groups, a composite equation was derived
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from the means of the available data to facilitate data interpretation in these populations.
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In the GLI, prediction equations were developed using the Lambda-Mu-Sigma (LMS)

method [41]. Through the LMS, the complex effects of explanatory variables on the
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dependent variable are modeled using splines, which vary the dependent variable

nonlinearly as a function of the explanatory variable.

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Currently, there is a general tendency to adopt the GLI equations [38] due to the

elaboration of data from multiethnic groups, the wide age range contemplated by the
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equations (3-95 years of age), the uniformity in comparing data from the international

literature, and the availability of limits of normality obtained using a z-score [42]. The

threshold of the FEV1/FVC ratio to determine AFL is based on 1.64 SDs instead of 5%

of the LLN, and the severity of FEV1 is established using SD and z-scores [34,43]. In

addition, the GLI equations were derived from cross-sectional data that were later

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 applied in longitudinal studies [44]. Use of these equations is encouraged because they

identify longitudinal changes in intra-individual and inter-ethnic spirometric parameters

and therefore improve the epidemiological analysis of respiratory risk factors [36].

The GLI lacks data from large populations, especially those from Africa, South

Asia, and Latin America. Although spirometry reference equations have been developed

for the Asian population, the analysis of the effects of migration on lung function in this

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population both within the geographical region and to Western countries is necessary to

provide comprehensive recommendations for a better interpretation of the results

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[45,46]. Another disadvantage attributed to the GLI is the lack of predicted values for

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PEF and other airflows, limiting the interpretation of the MEFV curve [38]. Notably,

the collection of GLI data is continuous via an active repository; therefore, new
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reference equations can be derived [38].

Another widely discussed issue is reference equations for older adults. Aging is
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accompanied by clinical challenges, including a sedentary lifestyle and the presence of

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respiratory symptoms, multimorbidity, and polypharmacy, which may significantly

affect baseline values [32,47,48]. By including age-related changes in lung function, the
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GLI approach creates an age-appropriate definition of respiratory impairment [49].

Limitations regarding the use of GLI equations in older adults include the need for
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greater representation of individuals aged >75 years and survival bias in the older

elderly [37,50]. Moreover, more data in the geriatric population are needed to develop
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age-appropriate updated criteria for test performance [50]. For these reasons, caution is

required when interpreting pulmonary function data in the geriatric population using

either the GLI or other reference equations.

In recent years, several studies evaluated the fit and applicability of GLI

equations in different populations, and the results are discordant [32,36,51–53]. Linares-

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 Perdomo et al. [53] compared predicted GLI values in different population groups in the

United States and found that differences in minimum and maximum height were higher

in older subjects. Brazzale et al. [54] reported that the effects of changing to GLI

equations on interpretation are minimal when changing from National Health and

Nutrition Examination Survey (NHANES III) equations and most significant when

changing from European Community of Steel and Coal (ECSC) equations. Using the

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GLI equations instead of the NHANES III equations, Embling et al. [55] observed a

change in diagnosis of lung disease in 5.9% of the individuals. Belo et al. [32]

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compared baseline values from the NHANES III and GLI. The lowest %FVC and

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%FEV1 values were obtained using GLI equations, and the prevalence of AFL was

higher using ECSC equations, whereas GLI equations indicated restrictive defects. GLI
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equations tend to recognize AFL less frequently than do NHANES III equations [43];

using the z-score, as recommended by GLI, changed the diagnosis category in 10.7% of
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the cases, and discordance was higher in individuals aged >65 years. Chaiwong et al.
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[56] evaluated the differences and agreements regarding spirometry results using the

GLI, NHANES III, Knudson, and Siriraj reference equations in the Thai population.
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Differentiation in both functional diagnosis and severity classification was significant

across the four reference equations (p < 0.001).

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5. What recent studies have added to the spirometry approach

Recent studies on spirometry have added information relevant to clinical practice.

Change in prevalence of COPD based on predicted equations [57–64], impact of

different definitions of AFL on mortality [65–67], role of spirometry in population-

based studies [68–70], and paradigm in the diagnosis of ACO [71] have been

extensively discussed.

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 For screening COPD patients, the Global Initiative for Chronic Obstructive Lung

Disease (GOLD) criteria underestimate and overestimate disease prevalence in young

and elderly adults, respectively, whereas LLN-based criteria are more accurate [7,8,57–

59]. Comparing FEV1/FVC fixed-rate and LLN-based criterion, Pothirat et al. [7]

showed that most underestimated individuals had clinical significance as related to

obstructive airway diseases and chronic respiratory symptoms, mostly associated with

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rhinitis. A recent study indicated that 6.0% and 4.2% of individuals were diagnosed

with AFL using the GOLD and GLI criteria, respectively, and the rate of overestimation

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using GOLD criteria increased with age, ranging from 25% of cases at 50 years to 54%

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at 70 years [60].

In addition to the limited applicability of reference equations, the diagnosis of

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COPD remains under discussion [61]. In a population-based study from Lenoir et al.

[62], only one-third of subjects with COPD were aware of the disease. This result
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highlights the known problem of underdiagnosis, which is higher for males, younger
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individuals, never and current smokers, those with a lower education, and those with no

previous spirometry [63]. In contrast, Lenoir et al. [62] observed that more than 50% of
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the individuals diagnosed with COPD had normal spirometric parameters, indicating the

occurrence of COPD misdiagnoses or the possibility that diagnosis was based solely on
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respiratory symptoms. Spero et al. [64] demonstrated that up to one-third of patients

diagnosed with COPD in the hospital setting might be misdiagnosed using spirometry.
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Factors that contribute to inaccurate COPD diagnosis include lower smoking load, high

body mass index, and comorbidities [64]. Heffler et al. [3] observed that only 69.5%

and 13.3% of patients with doctor-diagnosed asthma and COPD, respectively, had

functional abnormalities in spirometry tests. Another controversy in spirometry is

whether the different definitions of AFL (FEV1 <0.7 vs. FEV1 <LLN) affect the

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 prediction of mortality [65,66]. Torén et al. [67] found that AFL assessed with fixed-

rate or LLN definitions and assessed by NHANES III equations presented similar risk

predictions for all-cause mortality, cardiovascular mortality, and COPD mortality.

A recent study [68] evaluated the role of spirometry and fractional exhaled nitric

oxide (FENO) measures in predicting poor outcomes in 1,122 children with asthma and

indicated that repeated measures of %FEV1 better predicted worse asthma control and

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asthma exacerbation than did repeated FENO measurements. In a large cohort of

children with asthma, risk factors for exacerbation varied according to the seasons,

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although lung function impairment was associated with higher likelihood of

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exacerbations in all seasons [69]. Patients with asthma exhibited a significant

association between decreased FEV1/FVC ratio and acute exposure to particles ≤10 μm
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in spring or sulfur dioxide in autumn or winter [70].

Spirometry plays an essential role in the diagnosis of ACO. A recent study

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evaluated 11,923 participants and determined the prevalence and risk factors for ACO
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in six low- and middle-income countries (LMICs) [71]. The authors used spirometry as

a basis for diagnosis and indicated that ACO might be as prevalent and more severe in
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LMICs as in high-income countries, and exposure to biomass fuel smoke might be a

neglected risk factor.

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Spirometry is increasingly used to assess the adverse effects of occupational

exposure and sociodemographic variables [10]. In a study [72] using NHANES data
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from employed North American adults, the prevalence of spirometry-defined airflow

obstruction and COPD was 12.4% and 3.47%, respectively; moreover, the prevalence of

AFL was high in workers of occupations involving installation, maintenance, and

repair. Brakema et al. [73] conducted a spirometry-based prevalence study in a highland

(~2050 m) and lowland (~750 m) and showed that the prevalence of COPD and air

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 pollution in households were higher in the highland and were independently correlated.

Lowe et al. [74] used spirometry to follow up 4,826 smokers and observed that low

income was an independent predictor of decreased FEV1 and increased rate of airway

diseases. Agustí et al. [75] observed that early life events can affect health in later life.

In a transgenerational cohort analysis, low lung function in early adulthood may identify

people at risk of early comorbidities and premature death.

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Spirometry can assess the impact of lung function impairment on nonrespiratory

health conditions. Cognitive impairment is more common in individuals with impaired

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lung function [76]. Lutsey et al. [77] evaluated the link between lung function

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impairment and risk of dementia in a community-based cohort followed for 27 years.

Restrictive defects and, to a lesser extent, obstructive defects were associated with
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increased risk of dementia, including Alzheimer's disease-related dementia and

cerebrovascular dementia. Another study determined the prevalence of spirometric

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changes in patients subjected to cardiac CT to detect coronary artery disease (CAD)

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[78] and found that the risk of abnormal lung function was comparatively higher in

smokers, elderly, and patients with CAD.

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6. Technological advances in spirometry equipment

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In addition to the technological advancements in conventional spirometers, there has

been recent progress in office spirometers (OSs). The main advantages of OSs are lower
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cost and smaller size, although low precision in FVC measurements, difficulty of

calibration, inability to show MEVT and MEFV curves, and limited number of

predicted equations available to the user may limit their applicability [9,10].

Nonetheless, a study [79] comparing OS results with formal laboratory-based

spirometer (LS) results in subjects with symptomatic obstructive pulmonary disease

Information Classification: General

 found a significant correlation between OS and LS values for FEV1 and FVC;

furthermore, 87% of the subjects had concordant spirometry data for AFL. In 155

individuals with suspected COPD, the ROC curve for the FEV1 calculated by OSs

reached an area under the curve of 0.86 (95% CI: 0.78–0.92), whereas the Youden’s

index with a cut-off point of 0.70 for FEV1/FEV6 reached an area under the curve of

0.97 [80]. Tupper et al. [81] evaluated a cohort of patients with stage 3 and 4 COPD for

t
ip
6 months and indicated that home telemonitoring with OSs improved overall QoL. Watz

et al. [82] also used OSs to monitor patients with severe COPD in the home setting and

cr
observed that FEV1 began to decrease 2 weeks before the onset of exacerbation

us
symptoms and did not return to presymptomatic levels 8 weeks after the event.

In addition to maximum expiratory flow meters, pocket spirometers (PSs) can

an
measure FEV1 and FEV6. PSs are recommended for monitoring, not for diagnosing,

several diseases in the home setting. PS advantages include ease of use, portability, and
M

low cost. However, compared to standard spirometers, PSs are not sensitive enough to
ed

adequately detect mild airway obstruction and only measure effort-dependent

parameters, which are more variable. Therefore, a conventional spirometer should be

pt

used for abnormal test results [9,10]. Schermer et al. [83] used the prebronchodilation

FEV1/FEV6 ratio measured by microspirometry and indicated that although

ce

microspirometry improved the diagnostic yield for possible underlying COPD in

patients with respiratory symptoms who consulted general practitioners (GPs), most
Ac

patients with undiagnosed COPD remained undiagnosed by GPs.

In recent years, smartphone game-based assessment (SGA) has gained

popularity as a complement to laboratory assessments. SGA is a practical solution to

reduce costs and improve accessibility, convenience, and portability [84]. Joo et al. [85]

compared real-time SGA and classic LS parameters and found that SGA data were

Information Classification: General

 statistically significant and reliable when assessing lung function in patients with stroke.

Therefore, SGA may be a useful tool in clinical practice for pulmonary function

rehabilitation and follow-up of populations with multiple clinical conditions. Moreover,

some studies have shown that smartphone spirometry can effectively measure lung

function using only microphone audio data from a standard smartphone. Electronic

systems have been designed that allow the microphone to work as a flow sensor and

t
ip
record the exhaled air [86].

cr
7. Expert Opinion

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Although spirometry is the most relevant test for assessing pulmonary function and

screening overall respiratory health, its limited use and the high rate of misdiagnosis in
an
patients with suspected chronic lung diseases who are seen by primary care physicians

are concerning. Strategies to overcome this limitation include raising awareness about
M

PFTs in the primary care network, increasing access to spirometry, and implementing

measures that may assist GPs in interpreting spirometric patterns. These approaches
ed

may improve the diagnosis of respiratory conditions.

pt

In addition to diagnosing mild airway obstruction when the FEV1/FVC (or

FEV1/VC) ratio is within the normal range, the FEV3/FVC ratio may be incorporated
ce

into clinical practice because of its high specificity to exclude an SAD diagnosis. In

contrast, the FEV1/FEV6 ratio is a good alternative to the FEV1/FVC ratio for COPD
Ac

screening. In addition, some data points in MEVT and MEFV curves may be useful for

obtaining AFL indices and identifying individuals with obstructive defects who are

considered normal according to traditional criteria. Nonetheless, these measures need to

be further discussed in international guidelines on spirometry.

Information Classification: General

 One of the major advances in spirometry testing provided by the GLI Network

was producing standardized reference equations for spirometry. Another advantage of

GLI equations is the possibility of calculating z-scores, allowing clinicians to interpret

lung function results independently of anthropometric and demographic data, which

reduces the potential bias when using predicted values. A simple linear graph containing

measured values using z-scores relative to a normal distribution may aid in

t
ip
understanding the spirometry results. In addition, the wide adoption of a standardized

report format for spirometry by PFT equipment manufacturers and laboratories may

cr
improve interpretation, communication, and understanding of test results.

us
Despite the importance of FEV1/FVC, caution is required when using this ratio

in older adults and individuals with mild airway obstruction. This problem can be
an
partially solved by adopting GLI criteria to improve the precision of the diagnosis of

COPD; notably, the GOLD criteria overestimate COPD starting at the age of 50 years.
M

In asthma, changes in %FEV1 can be used to assess disease risk, and this parameter is
ed

more accurate than changes in FENO. Strategies to control the target sources of air

pollution are necessary for this group of patients because this control directly affects the
pt

spirometry results.

Spirometry is a promising evaluation tool in population-based studies. Some

ce

occupations, poverty and its consequences (respiratory exposure, limited access to

health services, and lack of awareness about the risks of smoking), and high altitude
Ac

may exacerbate chronic lung disease. Furthermore, low FEV1 and FVC values in middle

age appear to be associated with an increase in the likelihood of dementia with

advancing age. Therefore, effective public health policies may decrease the prevalence

of this condition in the general population.

Information Classification: General

 Given the underutilization of spirometry, the incorporation of new portable,

easy-to-use spirometers should be encouraged to improve the applicability of

spirometry and health care outcomes in individuals with chronic lung disease. Although

there are still several barriers to the widespread use of OSs, these devices, when

compared to LSs, appear to be accurate and reliable in individuals with previously

established obstructive pulmonary disease. However, pulmonary function should be

t
ip
carefully evaluated using LSs for diagnosing these clinical conditions.

Considering the rapid progress in the areas of information technology and

cr
artificial intelligence, spirometry advances point to two perspectives:

us
• The inclusion of new metrics derived from spirometric tracings using

computational tools can functionally identify individuals with structural

an
lung diseases who are not currently diagnosed using traditional criteria.

• The technological improvement of OSs, PSs, and smartphone-based

M

spirometry may allow the increased adoption of spirometry into clinical

ed

practice and in home telemonitoring of severely ill patients.

In the coming years, the increased use of GLI equations may help overcome
pt

many problems involving reference values. Nonetheless, two open issues for future

research remain:
ce

• Identify the significance of z-score borderline categories combined with

Ac

environmental exposure and disease symptoms to allow early

identification of individuals at increased risk of COPD; and

• Develop specific reference values for the geriatric population and

specific ethnic groups using robust samples.

Given the importance of several recently published epidemiological surveys,

additional spirometry-based prevalence studies are necessary. Further research on

Information Classification: General

 spirometry is needed to better understand the association of certain occupations,

geographical conditions, and social conditions with an increased risk of lung disease. In

addition to the effects of ethnicity and current smoking, income disparity appears to be

an important factor for the progression of chronic lung disease. Research should focus

on defining the spirometric criteria of the ACO more accurately and the possibility of

including biomass fuel smoke exposure in the diagnostic criteria of this condition.

t
ip
Funding

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This research was supported by the National Council for Scientific and Technological

us
Development (#304625/2016-7), Coordination for the Improvement of Higher

Education Personnel (Finance Code 001), and Foundation Carlos Chagas Filho
an
Research Support of the State of Rio de Janeiro (#E-26/202.679/2018).
M

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or
ed

entity with a financial interest in or financial conflict with the subject matter or
pt

materials discussed in the manuscript. This includes employment, consultancies,

honoraria, stock ownership or options, expert testimony, grants or patents received or

ce

pending, or royalties.
Ac

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise

to disclose.

Information Classification: General

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trial. NPJ Prim Care Respir Med, 28(1), 17 (2018).

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84. Silsupadol P, Teja K, Lugade V Reliability and validity of a smartphone-based

assessment of gait parameters across walking speed and smartphone locations:

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Body, bag, belt, hand, and pocket. Gait Posture, 58, 516–522 (2017).

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85. Joo S, Lee K, Song CA Comparative study of smartphone game with spirometry

for pulmonary function assessment in stroke patients. Biomed Res Int, 2439312
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(2018).

86. Viswanath V, Garrison J, Patel S SpiroConfidence: determining the validity of

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smartphone based spirometry using machine learning. Conf Proc IEEE Eng Med
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Biol Soc, 2018, 5499–5502 (2018).

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Figure 1. Maximal expiratory flow-volume curve (A) and maximal expiratory volume-

time curve (B). Note the peak expiratory flow (PEF) and the relationships of forced

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expiratory volume in the first second (FEV1), forced expiratory volume in the third

second (FEV3), and forced expiratory volume in the sixth second (FEV6) with forced
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vital capacity (FVC).
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Figure 2. The green line represents the data, while the red line represents the adjusted

curve. The calculation of the transition point is shown in A. The calculation of the

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breakpoint and the change in the volume from the maximum to the breakpoint

(transition distance) is shown in B. The parameter D (not shown) describes the rate of
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increase in volume. Adapted from [12] with permission.
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Figure 3. Data from the spirometry test for an individual whose functional parameters
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are within normality according to age, height, sex, and ethnicity. The arrows indicate

the points where the measures were obtained. FEV1 = forced expiratory volume in the
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first second; FVC = forced vital capacity; LLN = lower limit of normal; ULN = upper
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limit of normal. Adapted [Testing your lungs: spirometry. Breathe, 14(3), 257–260

(2018). No authors listed] with permission.

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Figure 4. Representation of a simplified report proposed by the American Thoracic

Society. Only the tabulation of the data and curves of an individual who underwent the
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test without bronchodilation is shown. FEV1 = forced expiratory volume in the first
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second; FVC = forced vital capacity; FET = forced expiratory time; GLI = Global Lung

Function Initiative; LLN = lower limit of normal. The slow vital capacity maneuver is
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not shown.
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Figure 5. Factors that affect lung function.
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