Eur Respir J 2009; 33: 1367–1373 DOI: 10.1183/09031936.00117508 CopyrightßERS Journals Ltd 2009 Effect of heliox breathing on flow limitation in chronic heart failure patients M. Pecchiari*, T. Anagnostakos#, E. D’Angelo*, C. Roussos#, S. Nanas# and A. Koutsoukou# ABSTRACT: Patients with chronic heart failure (CHF) exhibit orthopnoea and tidal expiratory flow AFFILIATIONS limitation in the supine position. It is not known whether the flow-limiting segment occurs in the *Istituto di Fisiologia Umana I, Universita` degli Studi di Milano, peripheral or central part of the tracheobronchial tree. The location of the flow-limiting segment Milan, Italy, and can be inferred from the effects of heliox (80% helium/20% oxygen) administration. If maximal #Dept of Critical Care and Pulmonary expiratory flow increases with this low-density mixture, the choke point should be located in the Services, Evangelismos General central airways, where the wave-speed mechanism dominates. If the choke point were located in Hospital, Medical School, University of Athens, Athens, Greece. the peripheral airways, where maximal flow is limited by a viscous mechanism, heliox should have no effect on flow limitation and dynamic hyperinflation. CORRESPONDENCE Tidal expiratory flow limitation, dynamic hyperinflation and breathing pattern were assessed in M. Pecchiari 14 stable CHF patients during air and heliox breathing at rest in the sitting and supine position. Istituto di Fisiologia Umana I via L. Mangiagalli 32 No patient was flow-limited in the sitting position. In the supine posture, eight patients exhibited 20133 Milan tidal expiratory flow limitation on air. Heliox had no effect on flow limitation and dynamic Italy hyperinflation and only minor effects on the breathing pattern. Fax: 39 0250315430 The lack of density dependence of maximal expiratory flow implies that, in CHF patients, the E-mail: [email protected] choke point is located in the peripheral airways. Received: July 31 2008 KEYWORDS: Chronic heart failure, dynamic hyperinflation, expiratory flow limitation, heliox Accepted after revision: November 19 2008 idal expiratory flow limitation (EFL) at rest viscous mechanism (as is the case in normal STATEMENT OF INTEREST has been detected in both sitting and subjects at low lung volume), the flow-limiting None declared. T supine spontaneously breathing patients segment is located in the peripheral airways [4]. with acute heart failure [1], and in patients with chronic heart failure (CHF) in the supine position The aim of the present investigation was to assess alone [2]. At present, it is not known whether, in whether the tidal EFL exhibited by CHF patients CHF, the choke point is located in the central or in the supine position is located centrally or peripheral part of the tracheobronchial tree. Such peripherally. To this end, the density dependence localisation can be accomplished by studying the of EFL was studied by replacing inspired air with density dependence of maximal expiratory flow, heliox, a gas mixture three times less dense than and, consequently, the mechanisms by which air. The effect of heliox was assessed in terms of tidal EFL develops. According to the wave-speed maximal expiratory flows, dynamic hyperinfla- theory, flow limitation results from the coupling tion and breathing pattern, as previously between airway compliance and convective described in patients with stable chronic obstruc- acceleration of gas [3]. Since the pressure drop tive pulmonary disease (COPD) [5]. due to convective acceleration is density-depen- dent, the wave-speed theory states that the MATERIALS AND METHODS maximal expiratory flow increases with decreas- Stable ambulatory CHF patients (n514; one ing gas density. Flow limitation can also result female) with a mean¡SEM age of 57¡3 yrs were from the coupling between airway compliance studied. No patient had been hospitalised within and viscous pressure losses [3]. If flow is limited the 20 days preceding the study. Heart failure by this viscous mechanism, the maximal expira- was defined as symptomatic left ventricular tory flow is not expected to change when gas dysfunction with a left ejection fraction of ,0.45 density changes. When the maximal flow is documented by bidimensional echocardiogra- limited at wave speed (as is the case in normal phy. The congestive heart failure was post- subjects at high lung volume), the flow-limiting ischaemic in nine patients. No patient exhibited European Respiratory Journal segment is located in the central airways. In peripheral oedema. Three patients were current Print ISSN 0903-1936 c contrast, when the maximal flow is limited by a smokers, three nonsmokers and eight ex-smokers. Online ISSN 1399-3003 EUROPEAN RESPIRATORY JOURNAL VOLUME 33 NUMBER 6 1367 HELIOX BREATHING IN CHRONIC HEART FAILURE M. PECCHIARI ET AL. At the time of the study, 12 patients were being treated with the inspiratory part of the flow–volume loop of the control and diuretics, eight with b-blockers and four with digoxin. On the test breaths was poor. Patients were classified as non-flow- experimental day, Weber class was determined using cardio- limited, if the application of NEP increased expiratory flow pulmonary exercise testing [6]. Three patients were Weber class over the entire range of the control tidal volume, or flow- -1 -1 A (maximal oxygen uptake (V’O2,max)of.20 mL?kg ?min ), limited, if the control and test expiratory flow–volume loops -1 -1 four Weber class B (V’O2,max of 16–20 mL?kg ?min ), five superimposed at least in part (fig. 1). Two or three breaths after -1 -1 Weber class C (V’O2,max of 10–15 mL?kg ?min ) and two Weber each NEP test, the subjects inspired to total lung capacity -1 -1 class D (V’O2,max of ,10 mL?kg ?min ). Predicted V’O2,max (TLC) for assessment of inspiratory capacity (IC), and align- were computed using Wasserman’s equations [7]. Patients with ment of tidal flow–volume curves with respect to TLC. IC was primary pulmonary, neurological or myopathic diseases were measured as the difference between TLC and the end- excluded. In particular, to avoid the possible confounding expiratory volume of the control breath, and used to assess effects of subclinical COPD, patients were also excluded if their changes in dynamic hyperinflation, an approach that has been forced expiratory volume in 1 s (FEV1)/forced vital capacity shown to be reliable in COPD patients [12]. In each patient and (FVC) was ,75% [8]. To this end, before the beginning of the condition, a minimum of four acceptable IC manoeuvres, and experiments, spirometry was performed using standard meth- NEP applications were performed. ods and procedures [9], using a mass flow sensor (Vmax 22; Under all experimental conditions, three FVC manoeuvres SensorMedics Co., Yorba Linda, CA, USA), with reference were performed and the breathing pattern was assessed over a values being those of the European Coal and Steel Community 3-min period. Dyspnoea was measured under each experi- [9]. The study was approved by the Ethics Committee of mental condition using a 100-mm visual analogue scale (VAS). Evangelismos General Hospital (Athens, Greece) and each patient gave informed consent. Data, presented as mean¡SEM, were analysed using a mixed between–within-groups ANOVA. The correlation between The severity of chronic dyspnoea was assessed using the MMRC score and routine spirometric measurements was modified Medical Research Council (MMRC) scale [10]. examined using the nonparametric Spearman rank correlation. Patients were investigated while breathing air and 10 min after Statistical significance was taken at a p-value of f0.05. equilibration with heliox. Measurements were carried out first in the seated and then in the supine position (after 10 min in RESULTS the supine position). Air and heliox breathing were performed Sitting breathing air in random order. Table 1 shows the anthropometric characteristics and baseline lung function of the patients in the sitting position. FVC, FEV1, The assessment of tidal EFL was carried out by means of the expiratory reserve volume (ERV) and IC were reduced negative expiratory pressure (NEP) method [11]. Subjects, compared to predicted values. In this posture, none of the wearing a nose clip, breathed quietly through a flanged patients exhibited tidal EFL. Dyspnoea at rest was modest, as mouthpiece, a heated pneumotachometer (3830A; Hans indicated by the low VAS score (12¡2 mm). The significant Rudolph, Kansas City, MO, USA) connected to a differential correlation coefficients of MMRC versus the respiratory pressure transducer (Celesco LCVR-0005; Raytech variables are shown in table 2. MMRC correlated with Instruments, Vancouver, BC, Canada) and a low resistance percentage predicted IC, FVC and FEV1 (p50.006, 0.009 and two-way valve (2600; Hans Rudolph). The expiratory port of 0.038, respectively), as well as with age (p50.042) and the valve was connected to a Venturi device and the percentage predicted V’O2,max (p50.001). inspiratory port to a shutter (RV-12; AeroMech Devices, Almonte, ON, Canada). The Venturi device was connected via a solenoid valve to a high-pressure source and a regulator Supine breathing air allowed for a pre-set pressure (-5 cmH2O) at the airway Shifting to the supine position caused the FVC to decrease opening that was measured with a pressure transducer (change (D) in FVC -0.20¡0.04 L; p,0.01) and, as expected, IC (Celesco LCVR-0100; Raytech Instruments). The shutter was to increase (DIC 0.42¡0.09 L; p,0.01), whereas breathing connected through a three-way stopcock to the ambient air or pattern remained unchanged. In this position, eight (57%) to a large plastic bag containing humidified heliox at ambient patients became flow-limited. These patients had lower ERVs ¡ temperature. The patient was unaware of the gas mixture they than the non-flow-limited patients (0.25 0.04 versus ¡ were breathing.