a b s t r a c t

Background: Previous meta-analyses have shown that ultrasound guidance is an effective technique for radial ar- tery catheterization. However, these reports neglected to include several non-English language studies. Therefore, an updated meta-analysis including more eligible studies was performed to assess the effectiveness of ultrasound-guided Radial artery catheterization.

Methods: Eligible studies were identified by systematically searching PubMed, EMBASE, Wanfang, and China Na- tional Knowledge Infrastructure literature databases. The outcome measure was the rate of first-attempt success. Two investigators identified the Randomized controlled trials for inclusion and independently extracted data from these RCTs. The quality of the included studies was evaluated using the Jadad score. The Relative risk for dichotomous outcomes and the 95% confidence intervals (CIs) were calculated and pooled using a random-effects model.

Results: Eleven RCTs involving 803 patients met the inclusion criteria. Ultrasound-guided radial artery catheter- ization was generally associated with a 47% improvement, as compared with the palpation technique, in terms of the rate of first-attempt success (RR, 1.47; 95% CI, 1.22-1.76; P b .0001). Specifically, the ultrasound-guided tech- nique significantly improved the rate of first-attempt success for adult (RR, 1.39; 95% CI, 1.13-1.72; P = .002) and pediatric (RR, 1.68; 95% CI, 1.15-2.47; P = .008) patients.

Conclusions: adult and pediatric patients benefited from ultrasound-guided radial artery catheterization in terms of the rate of first-attempt success. Given the potential bias and significant heterogeneity of the available data in the present study, further investigation is required to confirm the present findings and to identify other effects of the ultrasound-guided technique.

(C) 2014

Introduction

Radial artery catheterization is a well-established procedure that en- ables accurate hemodynamic monitoring and frequent arterial blood sampling. The procedure is widely used in the operating room, intensive care unit, and the emergency department. To date, 2 main techniques are used in radial arterial catheterization or puncture. The traditional technique relies on external landmarks and uses pulse palpation to guide the radial artery catheterization. However, the palpitation tech- nique has been associated with a low rate of first-attempt success [1].

? Funding: This work was supported by a project funded by a Taishan scholar of Shandong Province (Grant NO. ZR2012HM001).

?? Disclosure: The authors declare no conflict of interest.

* Corresponding authors. Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Binzhou Medical University, 661 Yellow River Rd, Binzhou 256603, China, Tel./fax: +86 543 3258728.

E-mail addresses: [email protected] (X.-Z. Wang), [email protected] (C.-J. Lv).

¹ These authors contributed equally to this work.

The development of ultrasound applications in medicine has led to the use of ultrasound guidance as a tool for central vein catheterization; the ultrasound-guided technique has increased success rates and decreased the rates of complications, as compared with the traditional palpation technique [2-4]. The American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists recommend ultra- sound as an effective rescue technique for arterial access; ultrasound can likewise identify the location and patency of suitable arteries for cannulation or procedural access [5].

Previously reported systematic reviews and meta-analyses [6,7] were based on aggregate data from Randomized controlled trials ; their findings suggested that ultrasound-guided radial artery catheterization is superior to traditional palpation in terms of an improved rate of first-attempt success. However, the previous reviews included RCTs that were exclusively written in English and mainly con- ducted in the United States and Europe. These previous meta-analyses neglected non-English language RCTs, especially those published in Chinese; the excluded RCTs could add to the existing Knowledge base. Therefore, we conducted an updated meta-analysis that incorporated

http://dx.doi.org/10.1016/j.ajem.2014.10.008

0735-6757/(C) 2014

Bias assessment“>all relevant studies, including the original research from China, to criti- cally assess the rate of first-attempt success of ultrasound-guided radial artery catheterization.

Methods

Data sources and literature search

A Comprehensive literature search for original research articles (dated up to June 2014) was conducted in PubMed, EMBASE, Wanfang (www.wanfangdata.com.cn), and China National Knowledge Infra- structure (www.cnki.net) databases using the following keywords: [(Doppler OR ultrasound OR ultrasonography) AND (radial artery catheter- ization OR radial Arterial puncture)]. The search was restricted to human subjects and RCTs, but no language restrictions were imposed. Addition- al manual searches were made to identify all potentially relevant studies from the references of the search results as well as the recommenda- tions of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists [5].

Study selection

The following selection criteria were applied: (i) population: only adult and pediatric patients with radial artery catheters or punc- tures were included; (ii) intervention vs control: the study compared 2-dimensional ultrasound guidance against traditional palpation;

(iii) outcome measures: the rate of first-attempt success was reported; and (iv) study design: RCT was used.

Data extraction and outcome measurement

We recorded the first author, year of publication, sample size, study population (setting), operator, and the catheter specifications for each included RCT. To evaluate the eligibility of these studies, the analytical data and trial quality information were independently extracted by 2 authors. The extracted information were entered into a standardized Excel file by one author and subsequently checked by another author. Any discrepancies were discussed until a consensus was achieved. The analytical data to be to be included in our meta-analysis but was missing from the original published studies were sought from

their authors. The rate of first-attempt success was defined as the out- come measure.

Quality and risk-of-bias assessment

The methodological quality of each included study was evaluated using the Jadad scale [8]. This scale is composed of 3 items that described the randomization (0-2 points), blinding (0-2 points), and the dropouts and withdrawals (0-1 points) in the RCTs. A score of 1 is awarded for each of the abovementioned points. An additional point is given when the appropriate method of randomization and/or blinding is specified. A score of 2 or lower indicates low quality, whereas a score of 3 or higher indicates high quality [9]. The risk of bias was measured using the Cochrane Handbook for Systematic Reviews of Interventions (Revman version 5.1.0, The Cochrane Collaboration 2011).

Statistical analysis

The Preferred Reporting Items for Systematic Reviews and Meta- Analyses statement was followed during the analysis [10]. Significant differences between RCTs were reported in terms of the relative risk (RR), with 95% confidence intervals (CIs) for dichotomous outcomes; results were pooled across studies using a random-effects model [11]. The heterogeneity across studies was tested using the I² statistic, a quantitative measure of inconsistency across studies. The heterogeneity of each study was classified as either low (I² = 25%-50%), moderate (I² = 50%-75%), or high (I² N 75%) [12]. If I² N 50%, the potential sources of heterogeneity were identified using sensitivity analyses conducted by sequentially excluding each study and investigating the influence of a single study on the overall pooled estimate. A subgroup analysis was performed based on differences among studies in terms of the pa- tient age (>=18 years vs b 18 years), sample size (>=100 vs b 100), and methodological quality (>=3 vs b 3). The publication bias was assessed using Begg funnel plot and Egger test [13].A value of P b .05 was consid- ered significant. The analysis of publication bias was conducted using Stata version 12.0 (Stata Corporation LP, College Station, TX). Other data and statistical analyses were combined and performed using Revman. 5.1.0 (The Cochrane Collaboration, Oxford, UK).

Fig. 1. Search strategy and flowchart of the meta-analysis.

Table 1

Main characteristics of RCTs included in the meta-analysis

Study/Country	No. of patients (ultrasound/ palpation)	Study population	Operator	Catheters	Study design/Jadad score
Levin et al	69 (34/35)	Adult	Anesthesia attending physicians	20-G intravenous	RCT/3
[16]/Israel		(cardiothoracic,	and residents with USG central	catheters
		abdominal,	venous catheter placement	(Venflon;
		neuro-, and	experience but with minimal	Becton Dickinson,
		vascular surgery)	USG arterial catheterization experience	Helsinberg, Sweden)
Shiver et al	60 (30/30)	>=18 y (from the	Attending physicians with experience	20-G Arrow	RCT/3
[18]/		emergency department)	of US-guided peripheral and	radial-artery
USA			Central venous lines, but without	catheterizationkit
			US-guided arterial catheters	(Arrow International Inc,
				Reading, PA)
Schwemmer et al	30 (15/15)	>=6-mo children	Anesthesiologists with experience	24-G cannulas	RCT/2
[17]/Germany		(for neurosurgery)	of >=20 pediatric arterial catheterizations	(Becton Dickinson,
				Helsinberg, Sweden)
Ganesh et al	152 (72/80)	b 18 y children	Pediatric subspecialty trainee	NA	RCT/2
[19]/USA		(abdominal, craniofacial,	anesthesiologists who had performed
		neuro-, orthopedic, and	b10 US-guided arterial cannulations
		thoracic surgery)	before the study
Mei et al	40 (20/20)	32- to 62-year-old patients	Anesthesiologists with experience	20-G or 22-G intravenous	RCT/2
[23]/China		(with traumatic injure)	more than 5 y of clinical work,	catheters (Insyte WTM;
			and more than 5 mo of US-guided	Becton Dickinson,
			vascular puncture	Franklin Lakes, NJ)
Bobbia et al	72 (37/35)	Adult patients with	One board-certified anesthesiologist	NA	RCT/3
[14]/France		general anesthesia	who had been trained in the ultrasound
Ishii et al	59 (59/59)a	Pediatric patients scheduled	technique in 20 patients before the study Trainees in anesthesiology with experience	24-G JELCO cannulas	Crossover
[15]/Japan		to undergo elective	of >=3 y of Clinical training and with	(Smiths Medical,	RCT/3
		cardiac surgery	US-guided central venous catheterization	Dublin, OH)
		for congenital heart disease
Liu et al	60 (30/30)	1-3 y children with	Anesthesia attending physicians with	22-G intravenous	RCT/3
[21]/China		elective surgery	experience N 4 y of US-guided radial artery	catheters
			and deep vein puncture	(Insyte WTM;
				Becton Dickinson, Singapore)
Ma et al	61 (30/31)	16- to 75-year-old patients	Anesthesia attending physicians with	20-G catheters	RCT/2
[22]/China		needing to monitor	experience of >=5 years of clinical training	(Terumo, Japan)
		arterial blood pressure	and with US-guided central
Hansen et al	40 (40/40)a	and blood gas analysis >=18-year-old	venous catheterization Anesthesiologists with experience	20-G radial-artery	Blinded
[20]/Denmark		patients scheduled	of 20 y in transesophageal and	catheterization	and
		for elective cardiac surgery	transthoracic ultrasonography and	kit(Becton Dickinson	crossover
			of 1 y in ultrasonography dynamic needle	Critical Care Systems,	RCT/5
			tip positioning, but without	Franklin Lakes, NJ)
			US-guided nerve blocks
Quan et al	160 (80/80)	28- to 78-year-old patients	Anesthesia attending physicians	NA	RCT/2
[24]/China		scheduled for hepatectomy	with experience
		and splenectomy	of >=4 y of US-guided artery and venous catheterization

US, ultrasound; USG, ultrasound guidance; NA, not applied.

^a Matched data (the radial arteries are matched as they belong to the same patient).

Results

Eligible studies and studies of characteristics

The initial search yielded 185 potential articles; 174 of these articles were excluded based on their titles and abstracts because they were duplicate studies or because of other reasons (Fig. 1). A final list of 11 full-text RCTs were selected for the meta-analysis [14-24]. Seven of the RCTs were published in English [14-20], and the remaining 4 were in Chinese [21-24]. The principal characteristics of the selected articles are provided in Table 1. The selected RCTs involved a total of 803 patients; these studies were published between 2003 and 2014. The sample sizes of these RCTs varied from 30 to 160. Among the 11 RCTs, 7 involved adult patients [14,16,18,20,22-24] and 4 in- volved pediatric patients [15,17,19,21]. Eight RCTs adopted 20-24 G catheters [15-18,20-23], whereas the remaining RCTs did not report the catheter type or size [14,19,24]. In addition, all the included RCTs reported training or experience with both forms of arterial puncture.

Quality and risk-of-bias assessment

The 2 authors agreed on every item of the Jadad scores. The mean (SD) Jadad score was 2.7 (0.9). The risk-of-bias analysis showed that only one study was both double blinded and described the method used to conceal allocation of patients [20]. Fig. 2 presents the risk-of- bias of the individual RCTs.

Meta-analysis of outcome measure

All the selected RCTs reported the rate of first-attempt success [14-24]. The aggregated results of these studies suggested that ultrasound-guided radial artery catheterization was associated with a sig- nificant improvement in terms of the rate of first-attempt success, as compared with the palpation technique (RR, 1.47; 95% CI, 1.22-1.76; P b

.0001; Fig. 3). Significant heterogeneity was observed among the selected studies (P = .005 for heterogeneity; I² = 60%). We subsequently per- formed sensitivity analyses to explore potential sources of heterogeneity. Further exclusion of each study did not alter the combined RR value.

Fig. 2. Risk-of-bias assessment.

However, it did cause the CI to change the width with a range from 1.41 (95% CI, 1.17-1.68; P = .0002) to 1.54 (95% CI, 1.37-1.74; P b .00001). Fur-

thermore, we performed subgroup analyses for the rate of first-attempt success; this step aimed to examine the effect of various exclusion criteria

according to the patient age, patient sample size, and the methodological quality of the combined estimates (Table 2). These exclusion criteria did not significantly alter the overall combined RR, which ranged from 1.32 (95% CI, 1.12-1.55; P = .001) to 1.73 (95% CI, 1.35-2.21; P b .0001).

Fig. 3. Forest plot of the meta-analysis of RCTs. Ultrasound guidance techniques are compared with traditional palpation techniques in terms of the rate of first-attempt success. Each block represents a study, and the area of each block is proportional to the precision of the mean treatment effect in that particular study. The horizontal line represents the 95% CI for the treatment effect in a study. The center of the diamond represents the average treatment effect across studies. The width of the diamond denotes its 95% CI. US, ultrasound.

Table 2

Subgroup analyses based on various exclusion criteria for the rate of first-attempt success

Outcome	n (N)	Ultrasound	Palpation	RR (95% CI)	P	I2 (%)	Heterogeneity P	Model
All included trials [14-24]	803 (11)	306/447a	210/455a	1.46 (1.31-1.63)	b.00001	60	.0005	Fixed-effects
High-quality trials (Jadad score >=3) [14-16,18,20,21]	360 (6)	171/230a	113/229a	1.47 (1.08-2.00)	.02	76	.0009	Random-effects
Low-quality trials (Jadad score b3) [17,19,22-24]	443 (5)	135/217	97/226	1.39 (1.21-1.59)	b.00001	0	.43	Random-effects
Large-scale trials (number N 100) [19,24]	312 (2)	82/152	65/160	1.32 (1.12-1.55)	.001	0	.45	Random-effects
Modest small-scale trials (number b100) [14-18,20-23]	491 (9)	224/295a	145/295a	1.52 (1.22-1.91)	.0003	65	.004	Random-effects
Adult patients [14,16,18,20,22-24]	502 (7)	216/271a	157/271a	1.38 (1.22-1.55)	b.00001	65	.008	Fixed-effects
Pediatric patients [15,17,19,21]	301 (4)	90/176a	53/184a	1.73 (1.35-2.21)	b.0001	51	.11	Fixed-effects

n, number of patients; N, number of trials.

^a Matched data (the radial arteries are matched as they belong to the same patient).

Publication bias

The results of the Begg and Egger tests suggested that there was no significant publication bias for the rate of first-attempt success among the included RCTs (Begg test, P = .533; Egger test, P = .340; Fig. 4).

Discussion

The primary purpose of the present meta-analysis was to update and critically evaluate the effects of ultrasound-guided arterial catheteriza- tion on patients. Our results suggested that ultrasound guidance, as compared with traditional palpation, was associated with significant improvements in adult and pediatric patients in terms of the rate of first-attempt success.

To the best of our knowledge, reviews and meta-analyses on ultrasound-guided arterial catheterization have been previously published [6,7,25,26]. One such meta-analysis was performed and published in 2011 by Shiloh et al [6]. Their study involved a total of

Fig. 4. Publication bias.

311 patients and included 4 RCTs. Their meta-analysis showed that ultrasound-guided radial artery catheterization improved the likelihood of a first-attempt success rate by 71%, as compared with traditional pal- pation techniques. The most recent systematic review and meta- analysis included 7 RCTs and enrolled 546 patients; this review was conducted by Gu et al [26] and published in 2014. Their analysis sug- gested that ultrasound-guided radial artery catheterization is an effec- tive and safe technique for patients. The meta-analysis of the present study suggested that ultrasound-guided radial artery catheterization dramatically increased the rate of first-attempt success in both adult and pediatric patients. Thus, our results are apparently similar to the previous meta-analyses [6,26]. However, we excluded one study [27] that was included in the meta-analysis by Gu et al [26] because the con- trol group received the Doppler-assisted technique instead of the tradi- tional palpation technique. We also added a high-quality RCT [20] to our meta-analysis. Furthermore, the previous meta-analyses neglected studies from China [21-24], which may have increased the selection bias. We do not believe that research from China is of lower quality than that from the United States and Europe. Therefore, we set rigorous inclusion criteria to produce robust results and included additional RCTs (involving a total of 361 patients) to increase the sample size and to improve the test performance.

The present analysis only focused on the rate of first-attempt success

because it was the most tangible outcome. This rate is the most convinc- ing indicator that can represent the effectiveness of ultrasound-guided radial artery catheterization. This point was similarly highlighted by the authors of a previous meta-analysis [6]. Multiple discrete Clinical end points were previously assessed by the RCTs and included in our meta-analysis. These end points are, namely, the number of catheters used, overall success, mean attempts or time to success, and the inci- dence of complications like hematoma. Given that the included RCTs did not use uniform criteria to define these end points, we could not formally combine the said end points in the present study. However, these clinical end points provide more compelling evidence of the tan- gible benefits for clinicians than simply increasing First-pass success [26]. Future studies should clearly define these important points, as pre- viously reported by the prior research. In addition, we believe that first- attempt success may not be equal to the minimum clinically important difference despite the fact that any amount of change greater than the minimum clinically important difference threshold is generally consid- ered meaningful or important [28].

Several limitations of the present meta-analysis should be taken into consideration. First, the 11 included RCTs have a high variation of pa- tient populations. Overestimation of the treatment effect usually occurs in smaller trials compared with larger samples. Second, considerable heterogeneity was observed among the included RCTs. The targeted population, the Experience level of the operators, catheter specifica- tions, and study design differed among these RCTs. The above- mentioned factors may cause heterogeneity and potentially influence the meta-analysis results. Furthermore, differences in ultrasonic instru- ments used in the RCTs may have affected the present results. Finally, the exclusion of missing and unpublished data from the RCTs may have led to selection bias.

Conclusions

To date, evidence in the literature implies that both adult and pedi- atric patients have benefited from ultrasound-guided radial artery cath- eterization in terms of the rate of first-attempt success. However, the selected data for inclusion in the present meta-analysis have potential bias and significant heterogeneity. Therefore, large-scale studies with improved designs should be conducted in the future to further confirm the current findings and to investigate other effects of the ultrasound- guided technique.

Acknowledgments

We would like to acknowledge the authors of the original articles who provided additional data and information about their work beyond what was included in their published articles.

References

1. Sandhu NS, Patel B. Use of ultrasonography as a rescue technique for failed radial artery cannulation. J Clin Anesth 2006;18(2):138-41.
2. Leung J, Duffy M, Finckh A. Real-time ultrasonographically-guided internal jugular vein catheterization in the emergency department increases success rates and reduces complications: a randomized, prospective study. Ann Emerg Med 2006;48(5):540-7.
3. Froehlich CD, Rigby MR, Rosenberg ES, Li R, Roerig PL, Easley KA, et al. Ultrasound- guided Central venous catheter placement decreases complications and decreases placement attempts compared with the landmark technique in patients in a pediat- ric intensive care unit. Crit Care Med 2009;37(3):1090-6.
4. Hind D, Calvert N, McWilliams R, Davidson A, Paisley S, Beverley C, et al. Ultrasonic lo- cating devices for central venous cannulation: meta-analysis. BMJ 2003;327(7411):361.
5. Troianos CA, Hartman GS, Glas KE, Skubas NJ, Eberhardt RT, Walker JD, et al. Special articles: guidelines for performing ultrasound guided vascular cannulation: recom- mendations of the American Society of Echocardiography and the Society Of Cardio- vascular Anesthesiologists. Anesth Analg 2012;114(1):46-72.
6. Shiloh AL, Savel RH, Paulin LM, Eisen LA. Ultrasound-guided catheterization of the radial artery: a systematic review and meta-analysis of randomized controlled trials. Chest 2011;139(3):524-9.
7. Gu WJ, Liu JC. Ultrasound-guided radial artery catheterization: a meta-analysis of randomized controlled trials. Intensive Care Med 2014;40(2):292-3.
8. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17(1):1-12.
9. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001; 135(11):982-9.
10. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339:b2700.
11. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7(3):

    177-88.

    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta- analyses. BMJ 2003;327(7414):557-60.

12. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315(7109):629-34.
13. Bobbia X, Grandpierre RG, Claret PG, Moreau A, Pommet S, Bonnec JM, et al. Ultra- sound guidance for radial arterial puncture: a randomized controlled trial. Am J Emerg Med 2013;31(5):810-5.
14. Ishii S, Shime N, Shibasaki M, Sawa T. Ultrasound-guided radial artery catheteriza- tion in infants and small children. Pediatr Crit Care Med 2013;14(5):471-3.
15. Levin PD, Sheinin O, Gozal Y. Use of ultrasound guidance in the insertion of radial ar- tery catheters. Crit Care Med 2003;31(2):481-4.
16. Schwemmer U, Arzet HA, Trautner H, Rauch S, Roewer N, Greim CA. Ultrasound- guided arterial cannulation in infants improves success rate. Eur J Anaesthesiol 2006;23(6):476-80.
17. Shiver S, Blaivas M, Lyon M. A prospective comparison of ultrasound-guided and blindly placed radial arterial catheters. Acad Emerg Med 2006;13(12): 1275-9.
18. Ganesh A, Kaye R, Cahill AM, Stern W, Pachikara R, Gallagher PR, et al. Evaluation of ultrasound-guided Radial artery cannulation in children. Pediatr Crit Care Med 2009; 10(1):45-8.
19. Hansen MA, Juhl-Olsen P, Thorn S, Frederiksen CA, Sloth E. Ultrasonography-guided radial artery catheterization is superior compared with the traditional palpation technique: a prospective, randomized, blinded, crossover study. Acta Anaesthesiol Scand 2014;58(4):446-52.
20. Liu GL, Zheng TH, Lv H. Value of ultrasound-guided radial artery catheterization in infant patients. Chin J Anesthesiol 2013;33(10):1272-3.
21. Ma D, Huang LJ, Wang YL, Shang LG. Clinical application of ultrasound guided radial arterial cannulation. Chin J Pract Med 2013;40(23):34-5.
22. Mei W, Jin CG, Zhang Y, Zhang CH, Luo AL, Tian YK. Comparison of ultrasound- guided and conventional radial artery cannulation in hemodynamically unstable pa- tients with traumatic injury. J Clin Surg 2011;19(3):199-201.
23. Quan ZF, Chi P, Zhang BH, Cao YH, Li X, Ma DM. Clinical effects of ultrasound guid- ance on radial artery puncture cathete. J Clin Anesthesiol 2014;30(1):56-7.
24. Shiloh AL, Eisen LA. Ultrasound-guided arterial catheterization: a narrative review. Intensive Care Med 2010;36(2):214-21.
25. Gu WJ, Tie HT, Liu JC, Zeng XT. Efficacy of ultrasound-guided radial artery catheter- ization: a systematic review and meta-analysis of randomized controlled trials. Crit Care 2014;18(3):R93.
26. Ueda K, Puangsuvan S, Hove MA, Bayman EO. Ultrasound visual image-guided vs Doppler auditory-assisted radial artery cannulation in infants and small children by non-expert anaesthesiologists: a randomized prospective study. Br J Anaesth 2013;110(2):281-6.
27. Kupferberg DH, Kaplan RM, Slymen DJ, Ries AL. Minimal clinically important differ- ence for the UCSD Shortness of Breath Questionnaire. J Cardpulm Rehabil 2005;25 (6):370-7.