Should We Measure the FEV1 or the Specific Resistance of the Airways? An Evaluation in Patients with Either COPD, Chronic Dyspnea or Chronic Cough

doi:10.4236/ojrd.2012.22005

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Open Journal of Respiratory Diseases, 2012, 2, 31-36

http://dx.doi.org/10.4236/ojrd.2012.22005 Published Online May 2012 (http://www.SciRP.org/journal/ojrd)

Should We Measure the FEV1 or the Specific Resistance of

the Airways? An Evaluation in Patients with Either

COPD, Chronic Dyspnea or Chronic Cough*

Kinga Simon1, Viviane De Maertelaer2, André Noseda1

1The Pulmonary Division, CHU Brugmann, Brussels, Belgium

2IRIBHN and Department of Biostatistics and Medical Informatics (SBIM), Université Libre de Bruxelles, Brussels, Belgium

Email: [email protected]

Received December 27, 2011; revised February 3, 2012; accepted February 13, 2012

ABSTRACT

Background: The purpose of this study was to evaluate the relative contribution of measuring the forced expiratory

volume in one second (FEV1) or the specific resistance of the airways (sRaw) in adults referred for chronic obstructive

pulmonary disease (COPD), chronic dyspnea or chronic cough. Methods: This was a prospective study of 321 subjects

referred for lung function testing, in a setting of routine clinical management, for suspicion of COPD (or follow-up of

known COPD), chronic dyspnea or chronic cough. The proportions of FEV1 values below the normal range and of

sRaw values above the normal range were compared using a Chi-square exact test of Fisher. Results: In the COPD and

chronic dyspnea groups, sRaw was as frequently abnormal as FEV1. In the chronic cough group, sRaw was increased in

56.5% of subjects, while FEV1 was decreased in solely 34.8% (p = 0.059). Conclusions: This study suggests that sRaw

may be a better tool than FEV1 to detect bronchial obstruction in patients presenting with chronic cough.

Keywords: Body Plethysmography; Chronic Cough; Specific Airway Resistance

1. Introduction

Spirometry is often considered as the gold standard for

determination of obstructive pulmonary disease. This

method has however several limitations, which has led to

resistance measurements used to clarify lung pathophysi-

ology [1]. In the recent years, there has been a progres-

sive disinterest in resistance measurements, at least in

adults. As an illustration, the 2005 American Thoracic

Society and European Respiratory Society statements did

not address resistance measurements [2]. In contrast,

resistance measurements are still considered to be par-

ticularly relevant in pediatric patients [3,4].

The present study was designed to evaluate the relative

contribution of measuring the forced expiratory volume

in one second (FEV1) or the specific resistance of the

airways (sRaw) in adults referred for lung function test-

ing (LFT) because of chronic obstructive pulmonary dis-

ease (COPD), chronic dyspnea or chronic cough. These

indications were chosen because the Belgian authorities

recently suggested that the usefulness of assessing airway

resistance is not proven in subjects with either COPD,

chronic dyspnea or chronic cough [5]. We hypothesized

that sRaw may be more sensitive than FEV1 in detecting

bronchial obstruction in these groups of patients. The

study was performed in a setting of routine clinical man-

agement and aimed to evaluate the percentage of subjects

with an abnormal test, namely a decreased FEV1 or an

increased sRaw.

2. Patients and Methods

2.1. Study Design

In the present study, we prospectively evaluated the sRaw

and the FEV1 in three groups of subjects (as defined un-

derneath) in a setting of routine clinical management.

The patients were referred by their physician for LFT

because of either COPD (group 1), chronic dyspnea (group

2) or chronic cough (group 3). The study protocol was

approved by the Ethics Committee of the CHU Brug-

mann and each subject gave written informed consent to

the analysis of his (her) lung function data.

2.2. Patients

The study was performed at the Pulmonary Division of

the CHU Brugmann between 26/10/2009 and 16/07/2010.

All males and females between 18 and 70 years old, re-

ferred for LFT because of COPD, chronic dyspnea or

chronic cough, were eligible provided they gave in-

formed consent and were able to perform technically

*Conflict of interes

: There is no conflict of interest.

K. SIMON ET AL.

acceptable spirometry and plethysmography. Exclusion

criteria included age less than 18 or more than 70, being

referred for LFT because of another diagnosis, being

unable to perform either spirometry or plethysmography,

as well as having any contra-indication to LFT (recent

heart attack or pneumothorax, recent ocular, abdominal

or thoracic surgery, suspicion of tuberculosis, severe

claustrophobia).

2.3. Constitution of Groups

The classification into three groups was made on basis of

the requests for LTF, written by the referring physicians.

Subjects were put into group 1 (COPD) when the request

mentioned a clinical suspicion of COPD or follow-up of

a known COPD. When the request mentioned several

respiratory diseases, subjects were included provided

COPD was listed as the first diagnosis (e.g. COPD plus

bronchectasis). Subjects were put into group 2 (chronic

dyspnea) and into group 3 (chronic cough) when the re-

quest respectively mentioned chronic breathlessness or

chronic cough as the first reason to perform LTF. Pa-

tients referred for LFT for other indications (e.g. preop-

erative work-up), or for several indications with another

diagnosis listed first (e.g. known lung fibrosis and

chronic cough) were not included.

2.4. Lung Function Testing

A Zan (Waldfenster, Germany) body plethysmograph

was used. Patients were instructed in the correct tech-

nique while the plethysmography door was open. During

the maneuvers, patients were asked to firmly seal their

lips around the mouthpiece. Airflow at the mouth was

displayed against box pressure and their relationship was

computed according to an automated procedure. Signals

were digitized over a period of five breaths, with a sam-

pling rate of 50 Hz. After correction for the thermal drift

induced by the subject’s heat production, a loop was ob-

tained and midpoints at flows of +0.5 (point A) and −0.5

l·s−1 (point B) were obtained. The slope of the line be-

tween points A and B defined the sRaw. At least two

technically satisfactory five breath-loops were obtained

and the reported sRaw was an arithmetical mean. Spi-

rometry was performed with the door of the box open.

The subject was instructed to slowly inspire up to the

total lung capacity and to subsequently expire a forced

vital capacity. In each subject, two to three technically

acceptable curves were obtained. Optimization of the

reading of the expiratory curves was performed as rec-

ommended by Peslin et al. [6]. The FEV1 was defined as

the volume exhaled in one second during the perform-

ance of the forced vital capacity maneuver. When a

bronchodilation or a provocation test was performed,

only the baseline values were retained for analysis.

2.5. Interpretation of Lung Function Data

To calculate the predicted values for FEV1, the regres-

sion equations of Quanjer et al. [7] were used. An indi-

vidual FEV1 value was considered as below the normal

range if it was lower than the mean predicted minus 1.64

× standard deviation (SD). The data of Pelzer and Thom-

son [8] were used as mean predicted values for sRaw,

depending on gender. An individual sRaw value was

considered as above the normal range if it was higher

than the mean predicted value plus 2 × SD.

2.6. Statistical Analyses

The variables recorded in the three groups were com-

pared using either an ANOVA procedure (means com-

parisons in case of continuous variables) or a Chi-square

exact test (proportions comparisons in case of discrete

variables). More particularly, the proportions of FEV1

values below the normal range and of sRaw values above

the normal range were compared using a Chi-square ex-

act test of Fisher. The analysis was made separately in

the three groups (COPD, chronic dyspnea, and chronic

cough). The statistical software used was SPSS version

17.0.

2.7. Retrospective Review of Medical Charts

Twelve months after the study had been completed, medi-

cal charts were examined to check for the final cause

retained for chronic dyspnea and for chronic cough, in

the chronic dyspnea and chronic cough groups.

3. Results

During the study period, 321 subjects were included. The

allocation into the three groups is listed in Table 1, as

well as the mean (SD) values obtained for FEV1 and

sRaw. COPD subjects were older than subjects with

chronic dyspnea or chronic cough. The proportion of

males in the COPD group was higher than in the chronic

dyspnea group, and tended to be higher (p = 0.074) than

in the chronic cough group. As expected, FEV1 was lower,

and sRaw higher, in the COPD group than in the other

two groups (Table 2).

Individual FEV1 values were plotted against predicted

values, separately in males and females. As shown in

Figure 1, measured values were predominantly under the

identity line in the COPD group, while a large proportion

of values were near the identity line in the chronic dysp-

nea and chronic cough groups (Figures 2 and 3). The

proportions of subjects with FEV1 within versus under

the normal range, as well as those of subjects with sRaw

within or above the normal range, are shown in Tab le 3.

In the chronic dyspnea and COPD groups, sRaw was as

frequently abnormal as FEV1 (exact Fisher test, p = 1.000

K. SIMON ET AL.

Table 1. Allocation of 321 subjects into three groups.

Group 1 (COPD)

n = 177

Group 2 (Chronic dyspnea)

n = 98

Group 3 (Chronic cough)

n = 46

Age (years) 58.1 (7.6) 46.5 (13.3) 50.0 (14.2)

Gender 114 M/63 F 45 M/53 F 23 M/23 F

FEV1 (% predicted) 53.0 (22.7) 81.1 (19.8) 84.9 (19.4)

sRaw (kPa.s) 3.21 (2.27) 1.44 (1.16) 1.44 (0.57)

M = males, F = females; Data in the table (continuous variables) are mean (SD).

Table 2. Comparison of age, gender, FEV1 and sRaw among groups, two by two.

COPD Chronic dyspnea COPD Chronic cough Chronic dypsnea chronic cough

Age (years) <0.001 <0.001 0.166

Gender 0.003 0.074 0.647

FEV1 (% predicted) <0.001 <0.001 0.590

sRaw (kPa.s) <0.001 <0.001 0.999

Data in the table are p values (Student t-test for age, FEV1, sRaw; Chi-square test for gender).

Table 3. Proportions of abnormal tests in 321 subjects.

Group 1 (COPD)

n = 177

Group 2 (Chronic dyspnea)

n = 98

Group 3 (Chronic cough)

n = 46

FEV1 normal 20.3% 59.2% 65.2%

Decreased 79.7% 40.8% 34.8%

sRaw normal 14.1% 59.2% 43.5%

Increased 85.9% 40.8% 56.5%

Figure 1. Measured values of forced expiratory volume in one second (FEV1) are plotted against predicted values, separately

in males and females, in the COPD group.

and p = 0.159, respectively). On the other hand, in the

chronic cough group, sRaw was increased in 56.5% of

subjects, while FEV1 was decreased in only 34.8% of

subjects; this difference reached near significance (exact

Fisher test, p = 0.059).

In the chronic dyspnea group, dyspnea remained un-

explained in 18 subjects (18%), including 10 subjects lost

for follow up. In the remainders, asthma, COPD, heart

failure and hyperventilation syndrome emerged as main

diagnoses (in, respectively, 32, 28, 7 and 6 subjects).

Less frequently, chronic dyspnea was ascribed to obesity

or beta blocker therapy (two subjects each) and to lung

K. SIMON ET AL.

Figure 2. Same legend as Figure 1, in the c hr onic dyspnea group.

Figure 3. Same legend as Figure 1, in the chronic cough group.

atelectasis, pericarditis or sarcoidosis (in a single subject

each). In the chronic cough group, cough remained un-

explained in 10 subjects (22%), including 5 subjects lost

for follow up. In the remainders, the main diagnoses

were cough-variant asthma, chronic rhinitis and sinusitis,

COPD, active smoking without COPD and post-infec-

tious cough (in respectively 12, 6, 4, 3 and 3 subjects).

Finally, angiotensin converting enzyme inhibitor-induced

cough, bronchectasis, gastroesophageal reflux and sar-

coidosis were diagnosed each in two subjects.

4. Discussion and Conclusions

Currently accepted indications for resistance measure-

ments include the evaluation of airflow limitation beyond

spirometry, the differentiation between different types of

obstructive pulmonary diseases having similar spiromet-

ric profiles, as well as the distinction of respiratory mus-

cle weakness from obstruction as the cause of low flow

rates [9]. In asthma, sRaw has been shown to be in-

creased in patients with no or few symptoms and normal

spirometric values [10]. In these particular patients, re-

sistance measurement is crucial to correctly diagnose

asthma. Similarly, the assessment of sRaw is useful in

patients with tracheal stenosis, compressive goiter or

other obstructive lesions of the larynx and the trachea

[11]. On the other hand, it is unknown whether measur-

ing sRaw in addition to FEV1 in patients with COPD,

chronic dyspnea or chronic cough caries relevant addi-

tional information. As sRaw is measured during tidal (or

near tidal) breathing maneuvers, it may reflect the func-

tional breathing status in current everyday life better than

FEV1, which is closer to breathing associated with

coughing, singing or laughing. Where lung pathophysi-

ology is concerned, sRaw is thought to predominantly

reflect the resistance of the large proximal airways [12].

Small distal airways may however contribute to some

extent, as sRaw is sensitive to a small airway disease like

bronchiolitis obliterans syndrome [13]. On these grounds,

it may be hypothesized that assessing sRaw may be rele-

vant in subject attending for COPD, chronic dyspnea or

chronic cough.

Determination of FEV1 has several advantages. Spi-

rometry requires only a simple equipment and FEV1

shows a rather good reproducibility. In our lung function

laboratory, the mean coefficient of variation of FEV1

amounts 5.0% in a population of COPD patients [14].

Furthermore, reduced FEV1 carries additional relevant

information, as FEV1 has been shown to be an inde-

K. SIMON ET AL. 35

pendent marker for cardiovascular mortality [15]. On the

other hand, spirometry is in a large extent dependent on

the subject cooperation. As an illustration, as many as

11.5% of subjects are unable to perform correct forced

expiratory maneuvers, even in a young population with

little or no chronic lung disease [16]. Similarly, measur-

ing sRaw via plethysmography has advantages and dis-

advantages. The equipment is more sophisticated, more

expensive and the reproducibility is somewhat weaker

than that of FEV1, with e.g. a mean coefficient of varia-

tion of 9.3% in COPD patients in our laboratory [14]. On

the other hand, sRaw is more sensitive than FEV1 in a

large variety of clinical conditions. Studying the acute

effect of physiotherapy on lung function in patients with

copious sputum production, Cochrane et al. found a

greater change in sRaw than in FEV1 [17]. In patients

with heart-lung or bilateral lung transplantation, Bassiri

et al found that serial measurements of sRaw were more

useful than those of FEV1 for early detection of bron-

chiolitis obliterans syndrome [13].

In the present study involving three groups of patients

with respectively COPD, chronic dyspnea and chronic

cough, we were able to show a larger proportion of sub-

jects with increased sRaw than that of subjects with de-

creased FEV1 only in chronic coughers. The difference

drew near statistical significance. On retrospective ex-

amination of medical charts, cough-variant asthma

emerged as the most frequent diagnosis retained to ex-

plain chronic cough. Cough-variant asthma is known to

be a frequent cause of chronic cough, particularly in non-

smokers. It may be either a precursor of typical asthma,

or persist lifelong as the sole symptom of asthma [18].

Definite diagnosis is usually based on both histamine or

metacholine inhalation testing and on resolution of cough

with anti-asthmatic therapy [19]. Studies on larger

groups of patients are needed to evaluate whether sRaw

may be a better tool than FEV1 to detect mild bronchial

obstruction in patients presenting with chronic cough.

5. Acknowledgements

The authors acknowledge Mrs F. Daimallah, Ch. Jacobs

and J. Roobaert for performing lung function testing, as

well as Mrs F. Martinez Vadillo for secretarial assis-

tance.

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List of Abbreviations

COPD: chronic obstructive pulmonary disease

FEV1: forced expiratory volume in one second

LFT: lung function testing

SD: standard deviation

sRaw: specific resistance of the airways