CJASN ePress. Published on September 22, 2016 as doi: 10.2215/CJN.

03890416
Article

The Agreement between Auscultation and Lung

Ultrasound in Hemodialysis Patients: The LUST Study
Claudia Torino, Luna Gargani, Rosa Sicari, Krzysztof Letachowicz, Robert Ekart, Danilo Fliser, Adrian Covic,
Kostas Siamopoulos, Aristeidis Stavroulopoulos, Ziad A. Massy, Enrico Fiaccadori, Alberto Caiazza, Thomas Bachelet,
Itzchak Slotki, Alberto Martinez-Castelao, Marie-Jeanne Coudert-Krier, Patrick Rossignol, Faikah Gueler,
Thierry Hannedouche, Vincenzo Panichi, Andrzej Wiecek, Giuseppe Pontoriero, Pantelis Sarafidis, Marian Klinger,
Radovan Hojs, Sarah Seiler-Mussler, Fabio Lizzi, Dimitrie Siriopol, Olga Balafa, Linda Shavit, Rocco Tripepi,
Francesca Mallamaci, Giovanni Tripepi, Eugenio Picano, Gérard Michel London, and Carmine Zoccali Due to the number of
contributing authors,
the affiliations are
Abstract provided in the
Background and objectives Accumulation of fluid in the lung is the most concerning sequela of volume expansion Supplemental
in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its Material.
reliability in ESRD is unknown. Correspondence: Prof.
Carmine Zoccali,
Design, setting, participants, & measurements In a subproject of the ongoing Lung Water by Ultra-Sound Guided Istituto di Fisiologia
Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomy- Clinica - Consiglio
Nazionale delle
opathy Trial, we compared a lung ultrasound–guided ultrafiltration prescription policy versus standard care in Ricerche and
high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the Nephrology, Dialysis
basis of 1106 pre– and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung and Transplantation
auscultation (crackles at the lung bases) and quantification of peripheral edema. Unit, Ospedali Riuniti,
c/o EUROLINE S.r.l.,
Via Vallone Petrara 57-
Results Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion 59, 89124 Reggio
as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for Calabria, Italy. Email:
repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) [email protected]
and k-statistics (k ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the
diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating
curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true
for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs.

Conclusions Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung
edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound
Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with
Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at
mitigating lung congestion in high-risk patients on hemodialysis.
Clin J Am Soc Nephrol 11: ccc–ccc, 2016. doi: 10.2215/CJN.03890416

Introduction when tested against thermodilution and shows a re-

In patients with ESRD, accumulation of fluid in the producibility even higher than that of this gold
lung is the most concerning consequence of volume standard in patients with heart disease. Further-
expansion, and the risk for pulmonary edema is very more, the same technique has also been extensively
high in this population (1,2). Systematic application of validated in patients on intensive care, in whom it
lung auscultation for the detection of crackles at the holds very high discriminatory power for identify-
bases of the lungs is recommended in clinical practice ing moderate and severe congestion (areas under
in both individuals with suspected heart failure (3) the receiver operating curves [ROCs] of 0.94 and
and patients with ESRD (4). However, the reliability 0.96, respectively) (9). In ESRD, the technique
of auscultation for the diagnosis of lung congestion shows high intra- and interobserver reproducibility
has never been assessed in this population. and also, high reproducibility when assessed with
Lung water can be reliably estimated in clinical diverse echo tomography machines (10). In ESRD,
practice by applying lung ultrasound (US) (5–8). Im- lung congestion as detected by lung US holds strong
portantly, lung US has been well validated as a prognostic power for death and cardiovascular
measure of pulmonary water in patients with cardio- events independent of traditional and ESRD–spe-
vascular disease (6), and it has virtually no bias cific risk factors (11,12).

www.cjasn.org Vol 11 November, 2016 Copyright © 2016 by the American Society of Nephrology 1
2 Clinical Journal of the American Society of Nephrology

This study was performed within the frame of the Lung congestion/edema (15). US-B lines measurements have a
Water by Ultra-Sound Guided Treatment to Prevent Death high interobserver reliability (concordance index =0.96) as
and Cardiovascular Complications in High Risk ESRD well as high interprobe concordance (concordance index
Patients with Cardiomyopathy (LUST) Trial (13), an ongoing =0.99) in patients on hemodialysis (10). US-B lines assess-
clinical trial testing the usefulness of systematic application of ment was made immediately before and after dialysis in
lung US in the clinical care of high-risk patients on hemodi- supine position. Scanning of the anterior and lateral chest
alysis. In this LUST Trial subproject, we have adopted lung was performed on both sides of the chest from the second
US as a reference method for testing the diagnostic reliability to the fourth (on the right side to the fifth) intercostal space
of pulmonary crackles as a clinical sign of pulmonary con- at parasternal to midaxillary lines as previously described
gestion and the prospectively collected, serial, well standard- (10). US-B lines were recorded in each intercostal space
ized (14) pulmonary auscultation data alongside with and defined as a hyperechoic, coherent US bundle at nar-
measurements of lung water by US. The diagnostic value row basis going from the transducer to the limit of the
of pulmonary auscultation for detecting moderate to severe screen. The sum of US-B lines produces a score reflecting
degrees of lung congestion was assessed by comparing the extent of lung water accumulation (5,6,16). Detailed
.1000 paired measurements of lung water by US with si- description of the technique is available in a 2-minute
multaneous standardized auscultation of the thorax. Because movie on YouTube (the incredible ultrasound lung comets;
pitting edema is frequent in patients with pulmonary crackles http://www.youtube.com/watch?v=7y_hUFBHStM).
attributable to heart failure and/or volume overload, a sec- Lung congestion was categorized according to the work by
ondary aim of this study was that of assessing whether the Frassi et al. (17) as absent: ,5 US-B lines; mild: $5 to ,15
combined detection of lung crackles and peripheral edema US-B lines; moderate: $15 to #30 US-B lines; and severe:
may improve the diagnostic performance of these physical .30 US-B lines. All nephrologists participating into the
signs for lung congestion. LUST Trial were trained by a specific web–based educa-
tional program (L. Gargani, et al., unpublished data) and
certified by the validation center at the Istituto di Fisiologia
Materials and Methods Clinica - Consiglio Nazionale delle Ricerche in Pisa, Italy.
The study protocol was approved by the ethical com- To be certified, assessors had to have an 85% or higher
mittees of the renal units participating in the LUST Trial. concordance in the assessment of lung US scans with the
All participants gave informed consent before enrolment. expert trainer at the validation center.

Patients Clinical Evaluation of Volume Status and Lung Auscultation

The LUST Trial is a multicenter, open, randomized, con- In all patients included into the active arm of the LUST
trolled trial aimed at assessing the usefulness of ultrasound B Trial, a standard pre– and postdialysis clinical evaluation
(US-B) lines in preventing adverse clinical outcomes (mortal- of volume status was done immediately before the US-B
ity, cardiovascular events, hospitalizations, and progression of lines measurements. Information about BP and BP changes
left ventricular hypertrophy and left ventricular dysfunction) over time, peripheral edema, presence/absence of dys-
in patients on dialysis at high cardiovascular risk. This trial is pnea, crackles on lung auscultation, interdialysis body
registered at ClinicalTrials.gov (identifier no. NCT02310061). weight gain, and body weight trajectory data over time
The inclusion criteria for the enrolment in the LUST Trial are was collected. Lung auscultation was carefully done in
age .18 years old; dialysis vintage .3 months; and a history anterior and posterior basilar sites in each hemithorax in
of myocardial infarction with or without ST elevation or un- the seated position. Patients were asked to perform peri-
stable angina, acute coronary syndrome documented by ECG odic, slow, deep respirations. To evaluate crackles, the fol-
recordings and cardiac troponins, or stable angina pectoris lowing scale (adapted from Kataoka and Matsuno [14])
with documented coronary artery disease by prior coronary was used: 1, no crackles; 2, I am uncertain about the pres-
angiography, electrocardiogram, or dyspnea class 3 or 4 New ence of fine crackles; 3, definite fine crackles at lung bases;
York Heart Association. Patients with cancer or other ad- 4, moderate crackles; and 5, bilateral, diffuse crackles. For
vanced noncardiac disease or comorbidity (e.g., end stage clinical edema, the following scale was used: 1, no clinical
liver failure) imposing a very poor short–term prognosis, ac- edema; 2, slight pitting (2-mm depth) with no visible dis-
tive infections or relevant intercurrent disease, or inadequate tortion; 3, somewhat deeper pit (4 mm) with no readily
lung scanning and echocardiographic studies were excluded detectable distortion; 4, noticeably deep pit (6 mm) with
from the trial. For the scope of this study, we focused on the dependent extremity full and swollen; and 5, very
patients randomized into the active arm (no pre- and post- deep pit (8 mm) with the dependent extremity grossly dis-
dialysis lung US is contemplated in patients in the control torted (18).
arm in the LUST Trial). This subproject included 79 patients
with simultaneous pre– and postdialysis US-B lines and pe- Statistical Analyses
ripheral edema and pulmonary crackles measurements. The Data are expressed as means6SD (normally distributed
total number of paired US lung scan and lung auscultation data), medians and interquartile ranges (IQRs; non–normally
records was 1106 (on average, 14 per patient) over an obser- distributed data), or percent frequencies (categorical
vation period of 11 months. data). The correlation between US-B lines and pulmonary
crackles/peripheral edema was assessed by using the
US-B Lines Measurement Pearson correlation coefficient, and the shared variance
US-B lines are the sonographic equivalent of classic B was calculated by squaring the same correlation coeffi-
lines detected in standard chest x-rays in patients with lung cient. To account for the fact that US-B lines were repeated
Clin J Am Soc Nephrol 11: ccc–ccc, November, 2016 Auscultation and Lung US in ESRD, Torino et al. 3

Table 1. Main demographic, anthropometric, and clinical characteristics in patients as divided according to ultrasound B lines
number

Ultrasound B Lines No.

P Value for
Characteristics of the Study Cohort
,5 $5 to ,15 $15 to #30 .30 Linear Trend

No. of patients 22 35 16 6
No. of paired ultrasound B lines 391 453 144 118
crackles/edema measurements
Age, yr 71611 74613 71613 68610 0.57
BMI, kg/m2 2765 2664 2464 2864 0.26
Men, % 73 71 50 33 0.15
Smokers, % 5 31 19 33 0.12
Patients with diabetes, % 43 33 38 67 0.48
On antihypertensive treatment, % 67 59 73 50 0.71
Dialysis vintage, mo 33 (10–71) 57 (34–282) 84 (33–150) 55 (39–85) 0.12
History of MI or stable angina pectoris 13 (59) 19 (54) 6 (38) 3 (50) 0.60
with documented coronary artery
disease without HF, n (%)
HF, NYHA class 3 or 4 without a history 3 (14) 2 (6) 5 (31) 1 (17) 0.11
of MI and/or coronary heart disease,
n (%)
History of MI/coronary heart disease 6 (27) 14 (40) 5 (31) 2 (33) 0.79
and HF, n (%)
Systolic BP, mmHg 139628 138624 145630 145621 0.84
Diastolic BP, mmHg 70613 69617 67612 72613 0.86
Pulse pressure, mmHg 69627 70622 78629 73616 0.69
Cholesterol, mg/dl 166642 165648 166650 149631 0.92
Hemoglobin, g/dl 11.161.2 11.261.3 11.060.9 10.060.9 0.24
Albumin, g/dl 4.060.7 3.760.3 4.060.8 3.460.5 0.15
Calcium, mg/dl 8.860.4 8.860.8 8.860.8 9.260.8 0.66
Phosphate, mg/dl 4.961.8 5.261.4 4.861.1 5.662.3 0.71
NYHA class 3 or 4, n (%) 6 (27) 9 (26) 5 (31) 3 (50) 0.67

BMI, body mass index; MI, myocardial infarction; HF, heart failure; NYHA, New York Heart Association.

measurements in the same patients, we performed weighted patients refers to the baseline assessment of US-B lines; the
regression analyses (19). The discrimination power of crack- number of paired US-B lines reported in Table 1 refers to the
les and peripheral edema for lung congestion as detected number of measurements falling in each category. Mean age
by US-B lines was investigated by analyzing the area un- was 72 years old, 65% of patients were men, and 20% were
der ROC curve. In this analysis, five categories of crackles current smokers; 37% of patients had diabetes, and all pa-
(14) or peripheral edema (18) (as described before) were tients had cardiovascular comorbidities. No differences in the
used to predict the presence of lung congestion as assessed other clinical data were found. These patients had been on
by lung US (mild: $5 to ,15 US-B lines; moderate: $15 to regular hemodialysis for a median time of 52 months (IQR,
#30 US-B lines; and severe: .30 US-B lines) (17). Sensitiv- 30–113) and were being treated with thrice weekly hemodi-
ity, specificity, and positive and negative predictive values alysis with various hemodialysis filters; 56% of patients were
of crackles and edema were also calculated. Pre- and post- treated with various antihypertensive drugs (32% of patients
dialysis variations of US-B lines were compared by the on monotherapy with calcium channel blockers, angiotensin
Wilcoxon test, and the relationship between pre- and post- converting enzyme inhibitors, sartans, a- or b-blockers, clo-
dialysis changes in crackles and peripheral edema was in- nidine, or furosemide; 36% of patients on double therapy;
vestigated by using the Wilcoxon test for dependent 18% of patients on triple therapy; and 14% of patients on
variables. The agreement between US-B lines and crackles/ multiple therapy with various combinations of these drugs).
edema was also described by using the Cohen k-coefficient.
Statistical analysis was performed by using standard sta- Association of Crackles and Peripheral Edema with Lung
tistical packages (SPSS for Windows, Version 20 [IBM Congestion as Measured by US-B Lung
SPSS, Chicago, IL] and MedCalc Software, Version 15 No patient had intercurrent inflammatory or infectious
[MedCalc, Ostend, Belgium]). broncopulmonary disease when simultaneous assessment
of US-B lines and crackles was done. Overall, 1106 paired
Results assessments (in 79 patients) of lung congestion by auscul-
The main demographic, anthropometric, clinical, and tation and lung US were performed. Thus, on average, each
biochemical characteristics of the study population at patient had 14 paired assessments. In 144 assessments
baseline are detailed in Table 1. The categorization of (13%), there was evidence of moderate congestion ($15 to
4 Clinical Journal of the American Society of Nephrology

#30 US-B lines), and in 118 assessments (11%), severe lung les/peripheral edema (see above), we found a poor agree-
congestion (.30 US-B lines) was documented. Overall, in the ment (by the k-weighted statistics) between US-B lines and
vast majority (61%) of these assessments, evidence of mod- pulmonary crackles in both analyses considering the aver-
erate or severe lung congestion by US was not accompanied age number of US-B lines and the average grading of crack-
by the presence of crackles. In severe lung congestion (as les and peripheral edema across the observation period
defined by US), the prevalence of crackles (49%) was higher or the whole series of measurements considered individu-
(P=0.003) than that registered in patients with moderate (by ally (Table 3).
US) congestion (31%). Table 2 shows the number of US-B
lines across crackles-number strata of increasing severity. Discrimination Analyses and Standard Diagnostic Tests
By the same token, peripheral edema was conspicuously On discriminant analysis (ROC curve), crackles had a
absent in as many as 87% and 80% of assessments where limited discriminatory power for the diagnosis of mild,
lung US indicated moderate and severe lung congestion, moderate, or severe lung congestion as assessed by US
respectively. The severity of lung congestion by crackles (mild lung congestion: area under the receiver operating
correlated very weakly with the severity of lung congestion curve [AUC] =0.61; 95% confidence interval [95% CI], 0.57
as detected by US-B lines (shared variance of 12%) (Figure to 0.64; P,0.001; moderate congestion: AUC=0.65; 95% CI,
1A). The correlation between peripheral edema and the 0.61 to 0.70; P,0.001; severe congestion: AUC=0.68; 95%
number of US-B lines was even weaker, and the shared CI, 0.62 to 0.74; P,0.001). Peripheral edema had virtually
variance was minuscule, being a mere 4% (Figure 1B). The no discriminatory power (mild lung congestion:
combination of crackles and edema (i.e., the sum of the AUC=0.51; 95% CI, 0.48 to 0.55; P=0.54; moderate conges-
two scores) did not improve the degree of the association tion: AUC=0.54; 95% CI, 0.50 to 0.58; P=0.05; severe con-
of these signs with US-B lines (shared variance of 10%). gestion: AUC=0.56; 95% CI, 0.50 to 0.62; P=0.03). The use
of a composite score (the sum of crackles and edema)
Postdialysis Changes of US-B Lines, Pulmonary Crackles, failed to materially increase the discrimination power of
and Peripheral Edema crackles and peripheral edema considered as separated
Lung congestion as detected by lung US was modified by physical signs (mild lung congestion: AUC=0.60; 95% CI,
dialysis treatment. The median number of US-B lines before 0.57 to 0.64; P,0.001; moderate congestion: AUC=0.65;
dialysis was nine (IQR, 5–19), and it fell to five (IQR, 2–10; 95% CI, 0.61 to 0.70; P,0.001; severe congestion:
P,0.001) after dialysis. In detail, the number of US-B lines AUC=0.68; 95% CI, 0.62 to 0.74; P,0.001). The sensitivity,
decreased in 79% of patients and did not change in 21% of specificity, and positive and negative predictive values of
patients (i.e., remained exactly the same or changed by two crackles and peripheral edema for lung congestion are re-
US-B lines at most). Before dialysis, in 39 of 79 patients ported in Table 4. In general, both clinical signs had very
(49% of patients) and a total of 439 assessments in the low sensitivity but high specificity for lung congestion.
same patients (79% of assessments), no crackles were de- However the false negative rate was exceedingly high
tected. Similarly, in 31 of 79 patients (39% of patients) and for both lung crackles and peripheral edema, ranging
495 assessments (90% of assessments) in the same patients, from 69% to 99% (Table 4). The likelihood ratios clearly
no peripheral edema was registered. In the remaining as- indicated that crackles and peripheral edema had modest
sessments (i.e., those where these alterations were noted), value for ruling in or out lung congestion.
both crackles (from a median predialysis score of 2.00
[IQR, 1.00–2.25] to a postdialysis score of 1.00 [IQR, Discussion
0.00–2.00]; P,0.001) and peripheral edema (from 1.00 This study shows that two time–honored clinical signs,
[IQR, 1.00–1.25] to 1.00 [IQR, 1.00–1.00]; P,0.001) reduced like lung crackles and peripheral edema, that are univer-
after dialysis. After dialysis, the degree of association of sally applied to detect and monitor volume excess and/or
crackles and peripheral edema with US-B lines remained fluid translocation to tissues and organs in disease states,
very poor (shared variances of 13% and 8%, respectively). including ESRD, have an unsuspectedly low sensitivity
for detecting interstitial edema in a most critical organ,
Agreement between US B Lines and Clinical Examination like the lungs, in this population. These findings have po-
In line with the previous analysis showing a modest tential implications for clinical practice and suggest that
shared variance between US-B lines and pulmonary crack- these clinical signs only remotely reflect the degree of

Table 2. Ultrasound B lines number across lung crackles strata of increasing severity

Ultrasound B Lines No.

Crackles Category Total
,5 $5 to ,15 $15 to #30 .30

0 370 388 88 60 906

1 13 35 7 6 61
2 6 26 24 37 93
3 1 3 3 4 11
4 1 14 9 11 35
Total 391 466 131 118 1106
Clin J Am Soc Nephrol 11: ccc–ccc, November, 2016 Auscultation and Lung US in ESRD, Torino et al. 5

Figure 1. | Poor correlation between ultrasound (US) B lines and clinical signs of lung congestion. Correlation between the severity of lung
congestion as detected by US-B lines with (A) pulmonary crackles and (B) peripheral edema.

lung congestion as measured by an objective, well vali- Patients with ESRD maintained on chronic dialysis have
dated method, like lung US scanning. an exceedingly high risk of hospitalization and death from
Lung auscultation is a cornerstone of physical examina- pulmonary edema (1), and the differentiation of congestive
tion. This procedure provides important clinical informa- heart failure from volume expansion may be problematic
tion about the respiratory system. Although expertise in in these patients (26). Lung congestion is an insidious phe-
auscultation requires standardization and specific training, nomenon that builds up gradually over weeks before
the technique is simple, low cost, and widely available, and frank, symptomatic pulmonary edema (27). Furthermore,
it can be repeated whenever required to monitor patients the degree of lung congestion only weakly associates with
(20). In patients with heart failure, the presence of crackles estimates of volume excess in ESRD, like total body water
is considered indicative of pulmonary congestion second- by Body Impedance Analysis BIA and interdialysis weight
ary to left ventricular dysfunction and/or volume over- gain/ultrafiltration volume (10). Subclinical congestion is
load, and this physical sign guides physicians to of peculiar relevance, because these patients have in-
implement or change therapy in patients with heart dis- creased alveolocapillary permeability (28), which make
ease (21). The presence of ankle edema and basal lung them vulnerable to volume overload that gradually builds
crackles helps to identify patients with suspected heart up during the dialysis interval. In this study, the median
failure who should be referred for echocardiography (3). number of US-B lines before a regular hemodialysis ses-
However, compared with imaging techniques, lung aus- sion was nine, and the IQR spanned from five to 19 lines.
cultation is notoriously insensitive to capture an increased These estimates underlie a median accumulation of water
quantity of fluid in the lungs in patients with acute heart in the lungs of about 1.2 L in a range comprised between
failure (22) and ambulatory patients with chronic heart 0.5 and about 2.2 L, which is a substantial degree of con-
failure (23,24), where the technique has both low sensitiv- gestion (6). Of note, the majority of these patients with
ity and low specificity as well (23). Furthermore, in the ESRD had no or very mild effort dyspnea, indicating
acute care setting, the diagnosis of interstitial edema by that clinical symptoms may be conspicuously absent,
auscultation is substantially inferior to those of chest radi- even at relevant levels of water accumulation in the
ography and lung US (25). lung. At peak of volume expansion (i.e., before dialysis),

Table 3. Agreement (weighted-k [95% confidence interval]) between ultrasound B lines and pulmonary crackles, peripheral edema,
and a combination thereof considering the individual average number of ultrasound B lines in the 79 patients and the simultaneous
average grading of crackles and peripheral edema or the whole series of measurements considered one by one (n=1106)

Individual Average US-B Lines Whole Series of US-B

Clinical Signs
Values, n=79 Patients Lines, n=1106

Pulmonary crackles 0.10 (0.01 to 0.20) 0.16 (1.13 to 1.20)

Peripheral edema 20.01 (20.11 to 0.09) 0.02 (20.01 to 0.04)
Crackles/edema 20.00 (20.02 to 0.01) 0.07 (0.05 to 0.09)

US-B, ultrasound B.
6 Clinical Journal of the American Society of Nephrology

crackles and peripheral edema were relatively rare, being

Table 4. Diagnostic value of pulmonary crackles and peripheral edema for the diagnosis of moderate and severe lung congestion in the 1106 paired measurements (in 79 patients) of these

The positive likelihood ratio (i.e., sensitivity-to-false positive rate ratio) of peripheral edema could not be calculated, because the corresponding false positive rates were zero. —, value cannot be
15/118 (13%)

957/988 (97%)
103/118 (87%)
15/46 (33%)

957/1060 (90%)
present just in 21% and 10% of patients, respectively. The

31/988 (3%)
Congestion
agreement between US-B lines and pulmonary crackles,

Severe
Lung

4.05

0.90
between the same parameter with peripheral edema, or
between a combination of crackles/edema was poor. As
one may expect from the relatively rare occurrence and the
Crackles and Edema

low sensitivity of lung crackles and peripheral edema, the

44/249 (18%)

832/857 (97%)
205/249 (82%)
44/69 (64%)

832/1037 (80%)
specificity of these signs for the diagnosis of lung conges-
25/857 (3%)
Congestion
Moderate

tion was very high indeed, but this high negative diagnos-
Lung

6.06

0.85
tic power was counterbalanced by almost equally high
false negative rates. Considering crackles and edema in
aggregate (which conforms to clinical practice and maxi-
mizes the discriminant power for lung congestion of these
200/644 (31%)
54/462 (12%)
408/462 (88%)
444/644 (69%)
200/254 (79%)

408/852 (48%)
signs), the combination of these two signs showed a satis-
Congestion
Mild Lung

2.66 factory to low positive predictive value (Table 4) (ranging

0.78
from 79% [mild congestion] to 33% [severe congestion])
and a high to moderate negative predictive power (rang-
ing from 90% [severe congestion] to 48% [severe conges-
tion]). However, this alteration went unnoticed in a
988/988 (100%)

3/3 (100%)
115/118 (97%)

988/1103 (90%)

substantial proportion of patients without crackles and/

Severe Lung

3/118 (3%)
0/988 (0%)
Congestion

or peripheral edema (false negative rate ranging from 69%

0.97
—

to 87%). Overall, the discriminant ability of crackles and

peripheral edema for the diagnosis of moderate and severe
lung congestion ranged from 0.54 to 0.68, which is a poor
discrimination power (29). Findings in this study support
Peripheral Edema

857/857 (100%)

3/3 (100%)

the contention that crackles and edema provide only mod-

246/249 (99%)

857/1103 (78%)
3/249 (1%)
0/857 (0%)
Congestion
Moderate

est information on interstitial edema in a critical organ,

Lung

0.99

like the lung, and reinforce the rationale underpinning

—

the LUST Trial (13). Lung US is a highly reliable, low–

cost, and easy to learn technique that can be performed
with whatever echotomographic machine is available
from a handheld one to echocardiography machines and
67/644 (10%)

423/462 (92%)
577/644 (90%)
67/106 (63%)

423/1000 (42%)
39/462 (8%)
Congestion
Mild Lung

machines applied for the sonography of abdominal organs

1.23

0.98

(8). The ongoing LUST Trial will establish whether system-

atic application of lung US may help preventing excessive
water accumulation in the lung and ultimately, improve
clinical outcomes in high-risk patients on dialysis.
This study has limitations. First, we repeatedly measured
964/988 (98%)
107/118 (91%)
11/35 (31%)

964/1071 (90%)
11/118 (9%)
24/988 (2%)
Severe Lung
Congestion

US-B lines and quantified crackles and peripheral edema in

3.84

0.93

patients in the active arm of a clinical trial enrolling patients

at high cardiovascular risk. Therefore, our results cannot be
generalized to the whole dialysis population. However, it is
precisely in this population that the risk of lung congestion
Pulmonary Crackles

is highest. Second, we focused on lung auscultation as

27/249 (11%)

838/857 (98%)
222/249 (89%)
27/46 (59%)

838/1060 (79%)
19/857 (2%)
Congestion

traditionally performed by standard stethoscopes by

Moderate
Lung

4.89

0.91

trained physicians. Novel acoustic devices for use at the

clinical signs and simultaneous ultrasound B lines

bedside are being proposed (e.g., electronic stethoscopes

synchronized with small recorders in the form of smart-
phone applications) to record lung sounds and enhance
the usefulness of auscultation (20). Therefore, the value
172/644 (27%)

434/462 (94%)
472/644 (73%)
172/200 (86%)

434/906 (48%)
28/462 (6%)
Congestion
Mild Lung

of these novel devices has potential for the detection of

4.41

0.78

lung congestion far superior to conventional auscultation.

Third, although the measurements of crackles and periph-
eral edema in the LUST Trial were well standardized and
performed with a high degree of attention by physicians,
Negative predictive

Negative likelihood

we have not specifically measured the interobserver vari-

False negative rate
Positive predictive

Positive likelihood
Diagnostic Value

False positive rate

ability of these clinical signs in the LUST Trial.

In conclusion, two classic physical signs, like lung
calculated.
Sensitivity

Specificity

crackles and peripheral edema, have a very low sensitivity

value

value

ratio

ratio

for detecting interstitial lung edema in patients with ESRD.

These findings reinforce the rationale underlying the LUST
Trial, a trial testing US-B lines as an instrument to guide
Clin J Am Soc Nephrol 11: ccc–ccc, November, 2016 Auscultation and Lung US in ESRD, Torino et al. 7

interventions aimed at mitigating lung congestion in high- 14. Kataoka H, Matsuno O: Age-related pulmonary crackles (rales) in
risk patients on hemodialysis. asymptomatic cardiovascular patients. Ann Fam Med 6: 239–245,
2008
Acknowledgments 15. Picano E, Gargani L: Ultrasound lung comets: The shape of lung
water. Eur J Heart Fail 14: 1194–1196, 2012
We thank Sarah Rocchi and Gennaro D’Angelo for their invalu-
16. Frassi F, Gargani L, Gligorova S, Ciampi Q, Mottola G, Picano E:
able support during the Lung Water by Ultra-Sound Guided Clinical and echocardiographic determinants of ultrasound lung
Treatment to Prevent Death and Cardiovascular Complications in comets. Eur J Echocardiogr 8: 474–479, 2007
High Risk ESRD Patients with Cardiomyopathy (LUST) Trial. 17. Frassi F, Gargani L, Tesorio P, Raciti M, Mottola G, Picano E:
The LUST Trial is a study entirely funded by the European Renal Prognostic value of extravascular lung water assessed with ul-
trasound lung comets by chest sonography in patients with
Association - European Dialysis Transplant Association. We thank dyspnea and/or chest pain. J Card Fail 13: 830–835, 2007
Nancy CHRU University Hospital, which sponsored the trial in the 18. Seidel HM, Ball JW, Dains JEBG: Heart and blood vessels. In:
French centers. Mosby’s Guide to Physical Examination, 3rd Ed., edited by
The LUST Trial collaborators can be found in the Supplemental Schrefer S, St. Louis, MO, Mosby, 1995, p 419
Appendix. 19. Neter J, Kutner MH, Nachtsheim CJ, Li W: Applied Linear Statistical
Models. Available at: http://www.jhs14.business.msstate.edu/bqa9333/
tips/15.70_TukeyMC_NeterKutner.pdf. Accessed April 6, 2016
Disclosures
20. Bohadana A, Izbicki G, Kraman SS: Fundamentals of lung aus-
None.
cultation. N Engl J Med 370: 744–751, 2014
21. Gopal M, Karnath B: Clinical diagnosis of heart failure. Hosp
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eureca-m/LUST_eureca-m.html. Accessed September 1, 2016 DCSupplemental.