HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Koulouris, N.G. Articles by Jordanoglou, J. Search for Related Content PubMed PubMed Citation Articles by Koulouris, N.G. Articles by Jordanoglou, J.

Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis

¹ Dept of Respiratory Medicine, Respiratory Function Laboratory, University of Athens Medical School, "Sotiria" Hospital, Athens, Greece. ² Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada

CORRESPONDENCE: N. G. Koulouris, Respiratory Function Laboratory, Dept of Respiratory Medicine, University of Athens, "Sotiria" Hospital for Diseases of the Chest, 152, Mesogion Ave, Athens, GR-115 27, Greece. Fax: 30 2107770423. E-mail: koulnik@med.uoa.gr

Keywords: bronchiectasis, exercise, high-resolution computed tomography, negative expiratory pressure, pulmonary function, respiratory mechanics

Received: December 5, 2001
Accepted December 12, 2002

	Abstract

TOP Abstract Methods Results Discussion References

 
In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output (WR_max)) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring.

Lung function, MRC dyspnoea, HRCT score, WR_max and FL were assessed in 23 stable caucasian patients (six males) aged 56±17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score. WR_max was measured using a cyclo-ergometer.

According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3) WR_max (% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score.

In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.

Bronchiectasis is characterised by irreversible destruction of airways, mainly related to chronic infection. Although this condition is presently rare in the developed countries, particularly North America, it is still common in the underdeveloped world where it causes considerable morbidity and mortality 1. Although an obstructive pulmonary defect is found in the majority of these patients, a mixed obstructive/restrictive defect is not uncommon 1–5. The disease presents with varying degrees of fibrotic and emphysematous changes due to chronic lung inflammation, which eventually lead to chronic respiratory failure and severe disability 1–5. Chronic dyspnoea is a common complaint 6 and exercise capacity may be reduced.

Patients with chronic obstructive pulmonary disease (COPD) exhibit chronic dyspnoea and reduced exercise capacity, mainly as a result of tidal expiratory flow limitation (FL), with concurrent dynamic hyperinflation and inspiratory loading due to intrinsic positive end-expiratory pressure (PEEP_i), and reduction of inspiratory muscle force 7–12. It is not known if tidal FL is present in patients with bronchiectasis nor if it plays a role in chronic dyspnoea and exercise limitation, except in patients with cystic fibrosis. In this condition, which is also characterised by bronchiectasis, tidal FL is seldom present at rest and, if absent, the Medical Research Council (MRC) dyspnoea score is low 13 and there is little or no impairment of exercise capacity 14.

Accordingly, in the present study on 23 stable patients with bilateral bronchiectasis (BB) the authors have assessed if expiratory FL is present during tidal breathing and if it is related to the severity of chronic dyspnoea (MRC scale), exercise capacity and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring.

	Methods

TOP Abstract Methods Results Discussion References

 
The study was performed on 23 caucasian patients with BB. No patient was a current or exsmoker. The diagnosis was based on clinical history and HRCT scans. Eleven patients had post-tuberculosis and 12 postinfective bronchiectasis. None of the patients underwent surgery concerning bronchiectasis or other thoracic disease. At the time of this study their clinical and functional state was stable for at least 4 weeks. According to sputum culture patients can be classified into the Pseudomonas aeruginosa (PA) group, i.e. six patients who were colonised with P. aeruginosa, and the non-PA group, i.e. eight patients colonised with "normal flora", seven Haemophilus influenzae, one Acinetobacter and one Serratia. All patients were familiar with routine respiratory measurements and dyspnoea evaluation. Patients with a history of COPD, asthma, sleep apnoeas, other concomitant lung disease, cardiovascular disorders, obesity and other serious acute or chronic disease were excluded. Cystic fibrosis was excluded on the basis of a sweat test. The study had the approval of the institutional ethical committee and informed consent was obtained from all patients.

The severity of chronic dyspnoea was rated according to the modified MRC chronic dyspnoea scale 15 (table 1). Forced spirometry was measured with a screen pneumotachograph (Screenmate; Erich Jaeger GmbH & Co., Höchberg, Germany). Total lung capacity (TLC) and its subdivisions were assessed with the helium-dilution method. Carbon monoxide transfer factor (T_L,CO) was determined by the single breath-hold method (Benchmark Transfer Test; PK Morgan, Rainham, UK). The predicted spirometric values, static lung volumes and T_L,CO are from the European Coal and Steel Community 17. The arterial oxygen and carbon dioxide pressures (P_a,O2 and P_a,CO2 respectively) were measured with a blood gas analyser (288 Blood gas system; Ciba-Corning, MA, USA).

View larger version (10K): [in this window] [in a new window]   Fig. 1.— Flow/volume loops of test breaths and preceding control breaths of two representative bronchiectatic patients with different degrees of flow limitation: a) not flow limited (patient no. 12); b) flow limited over <50% tidal volume (patient no. 21). Solid arrow: points at which negative expiratory pressure was applied and removed; open arrow: expiration.

Procedure
Immediately prior to the study, the severity of chronic dyspnoea was self-evaluated (table 1) and arterial blood gases were measured. Next, routine spirometry and tidal FL were assessed in a random order while seated upright in a comfortable chair or lying supine on a comfortable couch, at least 2 h after eating or drinking coffee. Patients were asked to breathe room air through the equipment assembly with the noseclip on. Each subject had an initial 10–15 min trial run, in order to become accustomed to the apparatus and procedure. The pneumotachogram was continuously monitored on the screen of the computer. When regular breathing had been achieved, a series of test breaths were performed, in which NEP (–3.5 cmH₂O) was applied at the beginning of expiration and maintained throughout the ensuing expiration. Figure 1 shows typical V'/V loops of NEP test breaths and preceding control breaths of two patients. In patient no. 12 application of NEP resulted in an increase in flow throughout the ensuing expiration, indicating absence of FL (NFL), while in patient no. 21 application of NEP did not increase the flow over the 44% of the control tidal volume (V_T) (FL=44% V_T).

An incremental symptom-limited exercise test was also performed by 15 of the 23 patients, using an electrically braked cycled ergometer (Model A1; Instrumenten Lode NV, Groningen, the Netherlands) and an automated cardiopulmonary exercise system (Benchmark Exercise Test; PK Morgan Ltd, Rainham, UK). After a 3 min warming-up period, patients cycled at 50–60 revolutions per minute with the external power increased in 1-min steps of 20 watts to the limit of their tolerance. Oxygen saturation, heart rate and arterial pressure were continuously monitored with a vital signs monitor attached to the metabolic chart (Monitor M-1; PK Morgan Ltd). The patients were encouraged during the exercise test to reach their maximum. In this way, their maximal mechanical power output (WR_max) was determined. The predicted normal values for WR_max were those of Jones 22. There was no evidence of bronchospasm in any of the patients during or after the procedure.

Statistical analysis
Values are presented as mean±sd. One-way analysis of variance (Student Neuman-Keuls test) was used, in order to make multiple comparisons for each parameter studied in the NFL, FL supine and FL seated and supine groups. The unpaired t-test was used to detect statistically significant differences of all parameters studied in postinfective versus post-tuberculosis, and PA versus non-PA BB patients. Pearson's correlation coefficients (r) and linear regression analyses were used to assess correlations of WR_max (% pred) and HRCT score to all variables studied, in order to ascertain which parameters correlated best. For the MRC dyspnoea score, since it is an ordinal categorical variable, the Spearman rank correlation coefficient (r_s) was calculated, as it is appropriate for such data. A p<0.05 was taken as statistically significant.

	Results

TOP Abstract Methods Results Discussion References

 
The anthropometric characteristics and baseline lung function data of the patients are given in table 3. Eleven patients had obstructive, nine mixed (obstructive/restrictive) and one restrictive lung defects, while two patients had lung function within the normal range. Fourteen patients were NFL, five were FL only supine and four were FL both seated and supine. Of the nine patients who were FL seated and/or supine, two had obstructive and seven mixed lung defects, while the patients with restrictive defect or normal lung function were NFL. Nine of the patients with obstructive lung defect were NFL.

In contrast, compared to the non-PA group, the PA patients had poor lung function (table 4). In addition, they had higher MRC, five-point FL and HRCT scores and a lower WR_max (% pred).

The MRC dyspnoea score correlated significantly with most respiratory variables studied, but the closest correlation was with the five-point FL score (r=0.85) and forced expiratory volume in one second (FEV₁) (% pred) (r= –0.76). The relationship of MRC score to five-point FL score and FEV₁ (% pred) are depicted in figure 2.

View larger version (11K): [in this window] [in a new window]   Fig. 2.— Relationships of a) Medical Research Council (MRC) dyspnoea score to forced expiratory volume in one second (FEV1) (% pred) and b) five-point flow limitation (FL) score. a) y=3.8–0.03*x±0.83, r=–0.76, p<0.0001 (n=23). b) y=1.1+0.9*x±0.61, r=0.85, p<0.00001 (n=23).

View larger version (9K): [in this window] [in a new window]   Fig. 3.— Relationship between maximum work rate ((WRmax) % pred) and Medical Research Council (MRC) dyspnoea score. The slope indicates that the dyspnoea score increases, on average, by one MRC unit per 16% decrease in WRmax (% pred). y=100.5–(15.2*x±8.3), r=–0.88, p<0.001 (n=15).

View larger version (11K): [in this window] [in a new window]   Fig. 4.— Relationship of a) forced expiratory volume in one second (FEV1) (% pred) and b) transfer factor of the lung for carbon monoxide (TL,CO) (% pred) to high-resolution computed tomography (HRCT) score in 23 patients with bilateral bronchiectasis. Patients with obstructive (), obstructive/restrictive (•), restrictive () pulmonary defect and no lung function abnormality () are shown. a) y=114.4–6.9*x±1.2, r=–0.77, p<0.001 (n=23). b) y=110.1–5.6*x±1.1, r=–0.76, p<0.001 (n=23).

	Discussion

TOP Abstract Methods Results Discussion References

Using the NEP technique, the current authors have assessed expiratory FL during resting breathing in 23 stable BB patients: 61% were NFL, 22% were FL only supine and 17% were FL both seated and supine. A higher prevalence of tidal FL has been previously reported in stable COPD patients, particularly in the sitting position (range 42–56% of total patient population) 11, 12, 18. This probably reflects: 1) the greater severity of airway obstruction in COPD patients (two of the NFL patients in the current study had normal lung function) and 2) the confounding effect of a restrictive pattern in the BB patients. In fact, expiratory FL during resting breathing is extremely rare in patients with restrictive respiratory disorders 23 and the single patient with a pure restrictive lung defect in this study was indeed NFL.

Medical Research Council dyspnoea
The MRC dyspnoea score correlated best with the five-point FL score (r²=0.72) and could explain 72% of its variance. In 117 stable COPD patients, the five-point FL score was also selected by stepwise logistic regression analysis as the best predictor of MRC dyspnoea score among the various independent parameters studied, which included the demographic characteristics, FEV₁, FVC and FEV₁/FVC 16.

In COPD patients, chronic dyspnoea, as assessed with the modified MRC scale, has been attributed mainly to dynamic pulmonary hyperinflation with concurrent inspiratory loading due to PEEP_i and reduction of inspiratory muscle force 12, 16. In view of the high prevalence of FL at rest, it is likely that PEEP_i also plays a role in eliciting dyspnoea in BB patients, particularly during exercise. In fact, the MRC dyspnoea levels were significantly higher in the FL than in the NFL BB patients, with the highest scores in the subjects who were FL both seated and supine (table 3). Unlike in COPD 11, in BB patients the correlation of MRC dyspnoea score to IC (% pred) was not as close as for the five-point FL score (r²: 0.42 versus 0.72). In contrast, the correlation of MRC dyspnoea score to FEV₁ (% pred) was closer in BB than in COPD patients (r²: 0.58 versus 0.14).

Exercise capacity
A very close correlation was found between WR_max (% pred) and MRC dyspnoea score (fig. 3). To the best of the present authors' knowledge, this is the first time that such a relationship has been explored. The high correlation probably reflects the fact that the MRC dyspnoea scale (table 1) is designed to assess exercise capacity rather than severity of dyspnoea per se. The close correlation of WR_max to MRC dyspnoea score is clinically useful because, at least in BB patients, it allows the prediction of the exercise capacity to a useful approximation when cyclo-ergometry is not available or contraindicated. In contrast to COPD patients 11, the correlation of WR_max (% pred) to IC (% pred) was poor, reflecting the confounding effects of the restrictive pattern present in 10 of the 23 BB patients studied.

High-resolution computed tomography score
Among all respiratory variables studied, the FEV₁ correlated most closely (r=–0.77) with the cumulative HRCT scoring. This is in line with previous findings 24, 25 and is not surprising because most of the nine morphological indices used by the HRCT scoring method of Bhalla et al. 21 (see Methods section) are focused on the airways. As shown in figure 4, the relationship between FEV₁ (% pred) and cumulative HRCT score did not differ appreciably among the BB patients with obstructive, restrictive or mixed pulmonary defect.

A close correlation for HRCT to WR_max (% pred) (r=–0.73) was also found which suggests that the HRCT scoring method used is not only closely correlated with FEV₁ but it also predicts to a useful approximation, exercise performance (r²=0.54). In contrast, the correlation of HRCT score to MRC dyspnoea (r²=0.41) and five-point FL score (r²=0.32) was not as good.

Practical implications
Although the MRC dyspnoea score correlated best with the five-point FL score, the correlation with FEV₁ was also close in BB patients. Thus contrary to COPD patients, in which FEV₁ is a poor predictor of exercise tolerance and chronic (MRC) dyspnoea, in patients with bilateral bronchiectasis the FEV₁ is a useful alternative predictor of these entities.

The very close correlation found between WR_max (% pred) and MRC dyspnoea score is clinically useful because the latter score provides a satisfactory prediction of WR_max when exercise testing cannot be performed because of lack of equipment, inability and/or refusal of the patient.

As expected, among all variables studied, the FEV₁ correlated most closely with the cumulative HRCT scoring. It should be noted, however, that in BB patients the cumulative HRCT score was <14 out of a maximum 25 points, even when FEV₁ was as low as 20% pred. This suggests that the HRCT scoring method used should be modified.

Finally, the results of this study confirm the association of P. Aeruginosa colonisation with poor lung function 26. Furthermore, the authors have shown that PA patients have significantly higher MRC and HRCT scores and a reduced WR_max.

Conclusions
The present results indicate that in bilateral bronchiectasis patients: 1) flow limitation is common at rest in sitting and/or supine positions, and is associated with more severe Medical Research Council dyspnoea; 2) exercise capacity is closely related to the degree of Medical Research Council dyspnoea; and 3) the high-resolution computed tomography scoring used correlates best with forced expiratory volume in one second.

	References

TOP Abstract Methods Results Discussion References

 

1. Kolbe J, Wells AU. Bronchiectasis: A neglected cause of respiratory morbidity and mortality. Respirology 1996;1:221–225.[Medline] [Order article via Infotrieve]
2. Pande JN, Jain BP, Gupta RG, Guleria GS. Pulmonary ventilation and gas exchange in bronchiectasis. Thorax 1971;26:727–733.[ISI][Medline] [Order article via Infotrieve]
3. Ip M, Lauder LJ, Wong WY, Lam WK, So SY. Multivariate analysis of factors affecting pulmonary function in bronchiectasis. Respiration 1993;60:45–50.[ISI][Medline] [Order article via Infotrieve]
4. Cherniack NS, Vosti KL, Saxton GA, Lepper MH, Dowling HF. Pulmonary function tests in fifty patients with bronchiectasis. J Lab Clin Med 1959;53:693–706.[ISI][Medline] [Order article via Infotrieve]
5. Cherniack NS, Carton RW. Factors associated with respiratory insufficiency in bronchiectasis. Amer J Med 1966;41:562–571.[CrossRef][ISI][Medline] [Order article via Infotrieve]
6. Smith IE, Jurriaans E, Diederich S, Ali N, Shneerson JM, Flower CDR. Chronic sputum production: correlations between clinical features and findings on high resolution computed tomographic scanning of the thorax. Thorax 1996;51:914–918.[Abstract]
7. Pepe PE, Marini JJ. Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction: the auto-PEEP effect. Am Rev Respir Dis 1982;126:166–170.[ISI][Medline] [Order article via Infotrieve]
8. Valta P, Corbeil C, Lavoie A, et al. Detection of expiratory flow limitation during mechanical ventilation. Am J Respir Crit Care Med 1994;150:1311–1317.[Abstract]
9. Tantucci C, Ellaffi M, Duguet A, et al. Dynamic hyperinflation and flow limitation during methacholine-induced bronchoconstriction in asthma. Eur Respir J 1999;14:295–301.[Abstract]
10. Sulc J, Volta CA, Ploysongsang Y, Eltayara L, Olivenstein R, Milic-Emili J. Flow limitation and dyspnoea in healthy supine subjects during methacholine challenge. Eur Respir J 1999;14:1326–1331.[Abstract]
11. Diaz O, Villafranca C, Ghezzo H, et al. Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest. Eur Respir J 2000;16:269–275.[Abstract]
12. Diaz O, Villafranca C, Ghezzo H, et al. Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal expiratory flow limitation at rest. Eur Respir J 2001;17:1120–1127.[Abstract/Free Full Text]
13. Goetghebeur D, Sarni D, Grossi Y, et al. Tidal expiratory flow limitation and chronic dyspnoea in patients with cystic fibrosis. Eur Respir J 2002;19:492–498.[Abstract/Free Full Text]
14. Regnis JA, Donnell PM, Robinson M, Alison JA, Bye PT. Ventilatory mechanics at rest and during exercise in patients with cystic fibrosis. Am J Respir Crit Care Med 1996;154:1418–1425.[Abstract]
15. Mahler DA, Harver A. Measurement of symptoms: the benchmark of treatment. Minimizing the effects of dyspnea in COPD patients. J Respir Dis 1987;8:23–34.
16. Eltayara L, Becklake MR, Volta CA, Milic-Emili J. Relationship between chronic dyspnea and expiratory flow limitation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;154:1726–1734.[Abstract]
17. Quanjer PhH, (ed). Standardized lung function testing. Report Working Party "Standardization of Lung Function Tests", European Community for Coal and Steel. Eur Respir J 1993;6:Suppl. 16, 1–100.
18. Koulouris NG, Valta P, Lavoie A, et al. A simple method to detect expiratory flow limitation during spontaneous breathing. Eur Respir J 1995;8:306–313.[Abstract]
19. Koulouris NG, Dimopoulou I, Valta P, Finkelstein R, Cosio MG, Milic-Emili J. Detection of expiratory flow limitation during exercise in COPD patients. J Appl Physiol 1997;82:723–731.[Abstract/Free Full Text]
20. Tantucci C, Duguet A, Similowski T, Zelter M, Derenne JP, Milic-Emili J. Effect of salbutamol on dynamic hyperinflation in chronic obstructive pulmonary disease patients. Eur Respir J 1998;12:799–804.[Abstract]
21. Bhalla M, Turcios N, Aponte V, et al. Cystic fibrosis: Scoring system with thin-section CT. Radiology 1991;179:783–788.[Abstract/Free Full Text]
22. Jones NL.. Interpretation of stage I exercise test resultsIn: Jones NL, ed. Clinical Exercise TestingWB Saunders, Philadelphia, USA, 1997; pp. 124–149.
23. Baydur A, Milic-Emili J. Expiratory flow limitation during spontaneous breathing. Comparison of patients with restrictive and obstructive respiratory disorders. Chest 1997;112:1017–1023.[Abstract/Free Full Text]
24. Roberts HR, Wells AU, Milne DG, et al. Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function tests. Thorax 2000;55:198–204.[Abstract/Free Full Text]
25. Wong-You-Cheong JJ, Leahy BC, Taylor PM, Church SE. Airways obstruction and bronchiectasis: Correlation with duration of symptoms and extent of bronchiectasis on computed tomography. Clin Radiol 1992;45:256–259.[CrossRef][ISI][Medline] [Order article via Infotrieve]
26. Evans SA, Turner SM, Bosch BJ, Hardy CC, Woodhead MA. Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa. Eur Respir J 1996;9:1601–1604.[Abstract]

This article has been cited by other articles:

				M. A. Martinez-Garcia, J.-J. Soler-Cataluna, M. Perpina-Tordera, P. Roman-Sanchez, and J. Soriano Factors Associated With Lung Function Decline in Adult Patients With Stable Non-Cystic Fibrosis Bronchiectasis Chest, November 1, 2007; 132(5): 1565 - 1572. [Abstract] [Full Text] [PDF]

				F. Santamaria, S. Montella, L. Camera, C. Palumbo, L. Greco, and A. L. Boner Lung structure abnormalities, but normal lung function in pediatric bronchiectasis. Chest, August 1, 2006; 130(2): 480 - 486. [Abstract] [Full Text] [PDF]

				C Newall, R A Stockley, and S L Hill Exercise training and inspiratory muscle training in patients with bronchiectasis Thorax, November 1, 2005; 60(11): 943 - 948. [Abstract] [Full Text] [PDF]

				P. M. A. Calverley and N. G. Koulouris Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology Eur. Respir. J., January 1, 2005; 25(1): 186 - 199. [Abstract] [Full Text] [PDF]

				E.A. Edwards, I. Narang, A. Li, D.M. Hansell, M. Rosenthal, and A. Bush HRCT lung abnormalities are not a surrogate for exercise limitation in bronchiectasis Eur. Respir. J., October 1, 2004; 24(4): 538 - 544. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Koulouris, N.G. Articles by Jordanoglou, J. Search for Related Content PubMed PubMed Citation Articles by Koulouris, N.G. Articles by Jordanoglou, J.