[ Education and Clinical Practice Original Research ]

Swimming-Induced Pulmonary Edema Diagnostic Criteria Validated by Lung Ultrasound

Maria Hårdstedt, MD, PhD; Claudia Seiler, MD; Linda Kristiansson, MD; Daniel Lundeqvist, MD; Cecilia Klingberg, MD; and Annika Braman Eriksson, MD

BACKGROUND: Despite the increasing popularity of open water swimming worldwide, swimming-induced pulmonary edema (SIPE) is a poorly recognized condition lacking established diagnostic criteria. RESEARCH QUESTION: The aim of this study was to identify diagnostic criteria of SIPE during a large open water swimming event. STUDY DESIGN AND METHODS: In this cross-sectional study, 17,904 individuals swam 1,000, 1,500, or 3,000 m in cold open water during Sweden’s largest open water swimming event in 2018 and 2019. Of 166 swimmers seeking medical attention for acute respiratory symptoms, 160 were included in the study. Medical history, symptoms, and clinical findings were collected. On-site lung ultrasound (LUS) was performed to verify pulmonary edema. RESULTS: Pulmonary edema was confirmed by LUS in 102 patients (64%); findings were unilateral in 11 (7%). Peripheral oxygen saturation was identified as a strong independent diagnostic test for pulmonary edema, with # 95% as the suggested cut off based on receiver-operating characteristic curve analysis (area under the curve, 0.893; P < .0001). Crackles on lung auscultation, predominantly over the anterior chest, identified 88% of patients with edema. Peripheral oxygen saturation # 95% or auscultation findings of crackles identified pulmonary edema with a sensitivity of 97% and a specificity of 86%. A specificity of 98% and a positive predictive value of 99% for LUS-verified pulmonary edema were reached if patients presented with both oxygen saturation # 95% and auscultation of crackles. INTERPRETATION: We suggest a clinical algorithm for diagnosis of SIPE for swimmers with acute respiratory symptoms during swimming in cold open water. Novel features of focally distributed edema in the anterior parts of the lungs, sometimes unilateral, add to this unique dataset of an underreported condition. CHEST 2020; 158(4):1586-1595

KEY WORDS: immersion pulmonary edema; lung ultrasound; SIPE; swimming; swimming- induced pulmonary edema

FOR EDITORIAL COMMENT, SEE PAGE 1329

ABBREVIATIONS: LUS = lung ultrasound; MMU = mobile medical FUNDING/SUPPORT: Financial support for the study was provided by unit; SIPE = swimming-induced pulmonary edema; SpO2 = peripheral the Center for Clinical Research Dalarna-Uppsala University and the oxygen saturation Center for Research and Development, Uppsala University/Region AFFILIATIONS: From the Department of Cardiology (Dr Hårdstedt) Gävleborg. and the Department of Anesthesiology and Intensive Care (Drs Seiler CORRESPONDENCE TO: Maria Hårdstedt, MD, PhD, Center for Clin- and Klingberg), Falun Hospital, Falun, Sweden; Center for Clinical ical Research Dalarna (CKF Dalarna), Nissers väg 3, 791 82 Falun, Research Dalarna-Uppsala University (Drs Hårdstedt and Seiler), Sweden; e-mail: [email protected] Falun, Sweden; Sandviken North Primary Health Care Center Copyright Ó 2020 The Authors. Published by Elsevier Inc under li- (Dr Kristiansson), Sandviken, Sweden; Center for Research and cense from the American College of Chest Physicians. This is an open Development, Uppsala University/Region Gävleborg (Dr Kristiansson), access article under the CC BY-NC-ND license (http:// Gävle, Sweden; Department of Internal Medicine (Dr Lundeqvist), creativecommons.org/licenses/by-nc-nd/4.0/). Mora Hospital, Mora, Sweden; and the Vansbro Primary Health Care DOI: https://doi.org/10.1016/j.chest.2020.04.028 Center (Dr Braman Eriksson), Vansbro, Sweden.

1586 Original Research [ 158#4 CHEST OCTOBER 2020 ] auscultation, together with desaturation, are often Take-home Point described. Diagnostic criteria for SIPE vary in published A clinical algorithm is presented for assessment of cases, from a merely descriptive definition based on patients with acute respiratory symptoms and symptoms, to well-defined clinical parameters and suspected swimming-induced pulmonary edema radiologic verification of pulmonary edema.4,6,9,10 during open water swimming. The algorithm iden- Reports of the condition are mainly case series of young fi fi ti es pulmonary edema, veri ed by lung ultrasound, athletic men and triathletes; large cohort studies are based on peripheral oxygen saturation and lung lacking.4,5,9 With the rising popularity of open water auscultation. swimming among recreational swimmers as well as professional athletes, increased knowledge on SIPE is 8,11-14 Immersion pulmonary edema was first described in crucial. divers in 1981 and later also reported among open water swimmers as swimming-induced pulmonary edema To evaluate diagnostic criteria for SIPE, we studied 160 (SIPE).1,2 The pathophysiology of SIPE is not fully swimmers with respiratory symptoms in a large cohort ’ understood, but central pooling of blood during of 17,904 individuals participating in Sweden s largest immersion in cold water in combination with heavy annual open water event. Our aim was to identify easily exercise contribute to increased pulmonary vascular assessed clinical criteria based on physical examination pressure and subsequent pulmonary edema.3 SIPE and presentation of symptoms. Lung ultrasound (LUS) fi predominantly occurs in otherwise healthy was performed on-site to con rm pulmonary edema. individuals.2,4,5 The condition usually resolves LUS is a valuable tool in the differential diagnostics of acute respiratory failure and is highly sensitive for spontaneously within 48 h, but life-threatening cases in 15-17 swimmers and fatalities in divers have been reported.4-7 detection of extrapulmonary lung water. In our SIPE is characterized by acute onset of cough and context, LUS was also an effective alternative to other radiologic equipment on-site during an open water dyspnea, sometimes accompanied by excessive sputum 18 and hemoptysis, when swimming in open water.6,8 event. Findings of crackles or wheezes/rhonchi on pulmonary

Subjects and Methods The location of auscultation findings (right/left chest, anterior/ posterior chest) was noted. Peripheral oxygen saturation (SpO ) Vansbrosimningen 2 and heart rate were measured by using a pulse oximeter (Nellcor Vansbrosimningen is the largest swimming event in Sweden, OxiMax N-65 and Nellcor PM10N; Covidien) and BP using a attracting approximately 10,000 swimmers yearly during a 3-day digital automatic BP monitor (Omron HEM-907; Omron weekend in July. It takes place in the municipality of Vansbro, O Healthcare Co. Ltd.). Sp 2 was noted after the pulse oximeters 239 m above sea level, in cold freshwater rivers (15 C-20 C). showed a waveform curve or gave a signal for a synchronized Participants (10 years or older), of both sexes, athlete swimmers as pulse registration. well as unexperienced swimmers swim distances of 1,000, 1,500, or 3,000 m. A vast majority of the swimmers (98% among the Ethical approval was received from the regional ethical review board in included patients) wore wetsuits. The on-site health care consists of Uppsala, Sweden (Dnr 2017/216 and 2017/216/1). All patients a first aid team along the riverside and a mobile medical unit provided written informed consent for participation. (MMU) at the finish area. Because Vansbro is located 78 km from the nearest hospital, all patients with medical needs were primarily Lung Ultrasound treated at the MMU on site. All patients with respiratory symptoms at the MMU were examined with LUS by two experienced consultant Study Population and Data Collection anesthesiologists. Ultrasound machines aimed for point-of-care The total numbers of participants (age $ 18 years) at examinations with a lung preset adjusted to a depth of 12 cm Vansbrosimningen were 11,010 in 2018 and 9,811 in 2019. Of these, were used (BK Medical Flex Focus 500 with a curved probe 2,917 individuals participated in the event both years. All patients [BK medical type 8823] of 2-6 MHz; BK Medical AB). Patients, aged $ 18 years seeking help at the MMU with acute onset of cough sitting in upright position, were scanned for four left chest and/or dyspnea commencing during or immediately following regions and four right chest regions: upper and basal anterior, swimming were eligible for the study. Medical history, information and upper and basal lateral.19 For each lung region, a clip of about the race, symptoms, and clinical findings were collected within 2 s was recorded and later independently reviewed by another approximately 10 to 60 min following swimming. Symptoms were physician in a blinded manner. The presence of three or more reported as “cough,”“dyspnea,”“increased sputum,” and/or B-line artifacts (B-lines) confirmed a positive region. Bilateral or “hemoptysis.” Patients were asked if they had aspirated water during unilateral presence of two or more positive regions of the four the race. Lung auscultation findings were reported as “normal anterior/lateral regions was defined as pulmonary edema in the breathing sounds,”“crackles,”“rhonchi,” or “other findings.” current cohort, and these patients were referred to as “LUS

chestjournal.org 1587 positive (þ).” Patients lacking this pattern of B-lines were further samples. Agreement between tests is presented as percentages and referred to as “LUS negative (–).” In 2019, two posterior regions Cohen’s kappa coefficient (l). The receiver-operating characteristic (upper and basal posterior) were additionally scanned on each curve was used to illustrate the diagnostic value of SpO2. Multiple side for all patients. Posterior regions were not included when logistic regression analysis was performed to valuate diagnostic defining pulmonary edema according to LUS. criteria. IBM SPSS Statistics for Windows, version 25.0 (IBM SPSS Statistics, IBM Corporation), and GraphPad Prism version 7.00 Statistical Analysis (GraphPad Software) were used for statistical analysis and graphic The c2 test was used for comparisons of categorical outcomes. For presentation. P values < .05 were considered statistically significant. continuous data, the unpaired Student t test or the Mann-Whitney U For comparisons of clinical findings between LUS (þ)andLUS(–) test were used for comparisons between two groups. The Wilcoxon patients, a P value < .006 was considered statistically significant based signed-rank test evaluated differences between two groups of related on Bonferroni correction due to multiple testing.

Results (P < .0001). The group with LUS-verified pulmonary Participants edema was on average older than the group without edema (47 vs 38 years; P < .0001). The most common Altogether, 166 individuals matched the inclusion criteria. self-reported co-morbidities were asthma or Five patients were excluded due to missing LUS data, and hypertension in both LUS (þ) and LUS (–) patients. two patients declined participation. We included 160 Four patients reported heart disease (two reported admissions for 158 individuals; two patients, who sought cardiac murmurs of unknown significance). None had medical attention at two different occasions, were included previously known ischemic heart disease or heart failure. twice. In 2018, a reference group of 48 swimmers (aged $ 18 years) completing the same swimming race without Symptoms and Clinical Findings respiratory symptoms was recruited. A majority of patients in both the LUS (þ) and LUS (–) groups reported cough and/or dyspnea as the only Pulmonary Edema According to LUS symptom (Fig 2, Table 1). Although cough was reported Of 158 patients (160 admissions), 102 were positive on to the same extent in both groups, dyspnea showed a LUS examination, and 58 were negative. No pathologic tendency to be more often reported by patients with artifacts other than B-lines were identified on LUS. pulmonary edema (P ¼ .015). Increased sputum and/or Pulmonary edema according to LUS was predominantly hemoptysis was associated with findings of pulmonary detected over the anterior compared with the lateral edema (P ¼ .003). None of the patients was reported as regions (P < .0001) (Fig 1A). The median number of disoriented at admission. The occurrence of self- positive regions for LUS (þ) patients was seven of eight reported water aspiration was similar in the LUS (þ) regions examined (interquartile range, 2). The and LUS (–) groups (P ¼ .33). None of the included interobserver agreement for LUS evaluation based on all patients had an episode of severe aspiration. Three LUS regions (n ¼ 2,004) was 97.5% with a k value of 0.94 (þ) patients and six LUS (–) patients presented with (95% CI, 0.92-0.96). Eleven patients with respiratory symptoms of chest pain (3% and 10%, respectively). symptoms were examined with B-lines predominantly in Pathologic lung auscultation findings were reported for one lung, as a sign of unilateral edema. Seven of these 90% of LUS (þ) patients and 19% of LUS (–) patients. patients had a distinct unilateral edema with three to For LUS (þ) patients, these findings were reported as four positive regions. In nine of 11 patients with crackles (84%), rhonchi (2%), or both crackles and unilateral pulmonary edema, the right lung was affected. rhonchi (4%). Crackles had a higher specificity (90%) In the reference group of 48 swimmers without cough or and positive predictive value (94%) for pulmonary dyspnea, one person had bilateral pulmonary edema on edema according to LUS compared with including also LUS examination, and one had unilateral pulmonary the findings of rhonchi only (data not shown). Of six edema. Scanning of posterior regions in 2019 showed patients presenting with rhonchi only, two were LUS that B-line artifacts were rare: only one posterior sector (þ), and both of these patients had an SpO < 95% at for one patient was positive among all 85 patients 2 admission. Crackles were noted in the majority of LUS screened. (þ) patients (84%; n ¼ 86) heard over the anterior Baseline characteristics for LUS (þ) and LUS (–) lung fields and in 46% (n ¼ 47) exclusively over the fi patients, as well as the reference group, are presented in anterior lung elds (Fig 1B). The median SpO2 in the Table 1. The distance swum was similar in both groups; LUS (þ) group was 92% compared with 98% in the however, more LUS (þ) patients discontinued the race LUS (–) group (P < .0001) (Table 1). Only three

1588 Original Research [ 158#4 CHEST OCTOBER 2020 ] A LUS - number of positive sectors 0.046 0.665 P < .0001

Anterior Lateral Anterior Lateral Anterior Lateral sectors sectors sectors sectors sectors sectors Reference group (n = 48) LUS (–) (n = 58) LUS (+) (n = 102)

0 1 2 3 4

B Auscultation findings of crackles 12% 2% 2% 3% 7% 4%

96% 90% 38% 46%

Reference group (n = 48) LUS (–) (n = 58) LUS (+) (n = 102)

Crackles No crackles Posterior Anterior Anterior + Posterior

Figure 1 – Localization of LUS and auscultation findings. A, Number of positive regions (three or more B-lines) assessed by LUS examination presented as four anterior and four lateral chest regions. Comparisons between related samples using the Wilcoxon signed-rank test. B, Lung auscultation of crackles reported for the anterior, posterior, or anterior þ posterior chest. Data are presented for patients with pulmonary edema according to LUS [LUS (þ)], without pulmonary edema [LUS (–)], and a reference group. LUS ¼ lung ultrasound.

– # individuals in the LUS ( ) group had an SpO2 auscultation of crackles were independently 95% (95%, 92%, and 85%, respectively); the patient associated with findings of pulmonary edema with ORs with SpO2 of 85% had previously known asthma. In the of 40 and 65, respectively, in a multiple logistic reference group, 46 of 48 individuals had normal lung regression model; the model was adjusted for age. fi auscultation ndings, and the SpO2 was on average Despite difference in frequencies of sputum and/or 98% after completing the race. hemoptysis between LUS (þ) and LUS (–) patients (Table 1), occurrence of sputum and/or hemoptysis fi Diagnostic Criteria of SIPE failed as a predictor of LUS-veri ed pulmonary edema in the adjusted model. Interestingly, all patients SpO was a strong diagnostic test for pulmonary edema 2 presenting with sputum and/or hemoptysis in addition based on receiver-operating characteristic curve analysis to auscultation of crackles or SpO # 95% had (area under the curve, 0.893; 95% CI, 0.838-0.948; P < 2 pulmonary edema on LUS. .0001) (Fig 3). The optimal cut off level of # 95% in

SpO2 for LUS edema was based on sensitivity and A diagnostic algorithm for SIPE diagnosis was suggested fi fi # speci city tradeoff (Youden index, 176). Using the (Fig 5). Clinical ndings of SpO2 95% or auscultation finding of pulmonary edema according to LUS as of crackles identified LUS-verified pulmonary edema outcome, the diagnostic value of the following clinical with a sensitivity of 97% and a specificity of # criteria was assessed: (1) SpO2 95%; (2) crackles on 86% (Table 3). Based on this algorithm, all but three lung auscultation; and (3) sputum and/or hemoptysis patients with LUS-verified edema were identified (Fig 4). (Fig 4, Tables 2 and 3). Saturation # 95% and A combination of both these clinical criteria increased

chestjournal.org 1589 TABLE 1 ] Background Characteristics and Clinical Findings for LUS (þ) and LUS (–) Patients With Respiratory Symptoms and for a Reference Group With No Respiratory Symptoms

Patients With Cough and/or Dyspnea Variable LUS (þ)(n¼ 102) LUS (–)(n¼ 58) P Valuea Reference Group (n ¼ 48) P Valueb Baseline characteristics Age, mean SD, y 47 10 38 12 42 15 Sex, No. (%) Male 8 (8) 10 (17) 15 (31) Female 94 (92) 48 (83) 33 (69) Medical history, No. (%) Smoker 1 (1) 2 (3) 1 (2) Respiratory disease 19 (19) 21 (36) 3 (6) Asthma 18 (18) 20 (34) 3 (6) Heart disease 3 (3) 1 (2) 3 (6) Hypertension 11 (11) 4 (7) 1 (2) Factors concerning the race, No. (%) Distance 1,000 m 43 (42) 16 (28) 8 (17) 1,500 m 12 (12) 9 (15) 1 (2) 3,000 m 47 (46) 33 (57) 39 (81) Discontinuation of the race 45 (44) 5 (9) 0 Clinical findings Symptoms, No. (%) Aspiration during the race 45c (45) 30c (53) .329 12 (25) .006 Cough 79 (77) 43 (74) .636 Dyspnea 77 (75) 33 (57) .015 Increased sputum 32 (31) 6 (10) .003 Hemoptysis 3 (3) 0 NA Clinical findings Cyanosis, No. (%) 20e (20) 1 (2) NA 1d (2) NA d SpO2, % 92 (6) 98 (2) < .0001 98 (2) < .0001 Respiratory rate, breaths/min 20f (6) 20g (8) .758 20e (7) .155 Systolic BP, mm Hg 129d (25) 125 (25)e .292 127 (17) .979 Heart rate, beats/min 96c (22) 107 (23) < .0001 101 (19) .596 Lung auscultation, No. (%) Normal 10 (10) 47 (81) 46 (96) Crackles only 86 (84) 6 (10) 2 (4) Crackles þ rhonchi 4 (4) 0 0 Rhonchi only 2 (2) 4 (7) 0 Other findings 0 1 (2)

Median and interquartile range (IQR) are given if not otherwise stated. LUS ¼ lung ultrasound; LUS (þ) ¼ patients with pulmonary edema according to

LUS; LUS (–) ¼ patients with no pulmonary edema according to LUS; NA ¼ not applicable due to small sample size; SpO2 ¼ peripheral oxygen saturation. aComparison between LUS (þ) and LUS (–) patients; Student t test or Mann-Whitney U test for continuous variables; c2 test or Fisher exact test for categorical variables. The level for significance was set to .006 after Bonferroni correction for multiple comparisons. bComparison between the reference group and LUS (þ) and LUS (–) patients; Student t test or Mann-Whitney U test for continuous variables; c2 test or Fisher exact test for categorical variables Missing values: cn ¼1; dn ¼ 2; en ¼ 3; fn ¼ 6; gn ¼ 7.

1590 Original Research [ 158#4 CHEST OCTOBER 2020 ] 100 based on objective verification of pulmonary edema n = 23 n = 13 n = 16 n = 6 n = 3 (Fig 5). This is the largest group of swimmers presented 80 n = 29 thus far with LUS-verified pulmonary edema during an open water swimming event. There are a few reports of 60 n = 31 n = 20 pulmonary edema verified by LUS in breath-hold divers, but only one previous case report on SIPE.20-22 A 40 n = 19 strength of the study is the generalizability based on a

Percentage (%) Percentage large heterogeneous population of swimmers, including 20 all ages, both sexes, and various levels of swimming

0 skills. Diagnostic Criteria

Cough only In addition to acute onset of characteristic symptoms Dyspnea only (cough, dyspnea, excessive sputum, and/or hemoptysis) during swimming in open water, we suggest two clinical # Cough and DyspneaCoughIncreased onlyand/or Dyspnea sputum only+ criteria for SIPE diagnosis: SpO2 95% and/or lung Cough and/or Dyspnea and/or auscultation findings of crackles (Fig 5). These two Increased sputum + Hemoptysis criteria identify pulmonary edema with a high sensitivity based on LUS examination. Based on our data, the LUS (–) LUS (+) occurrence of pulmonary edema in a group with acute Figure 2 – Respiratory symptoms reported by patients. Symptoms were respiratory symptoms during swimming in cold open recorded as cough, dyspnea, increased sputum, and/or hemoptysis. Data water is high, and the suggested algorithm will obtain a are presented as percentage in each category for LUS (þ) patients and LUS (–) patients. See Figure 1 legend for expansion of abbreviations. desired high negative predictive value at the first clinical evaluation. In clinical application, findings of both the specificity for LUS (þ) to 98% with a subsequent crackles and saturation # 95% identify pulmonary decrease in sensitivity to 74%. edema based on LUS with a high positive predictive value (99%), whereas patients lacking both these criteria Discussion do not have edema (negative predictive value, 94%). For To the best of our knowledge, this study is the first patients with respiratory symptoms and one of the two structured evaluation of clinical diagnosis of SIPE in clinical criteria, we suggest LUS for differential open water swimmers with acute respiratory symptoms, diagnostics if available. Further monitoring and

100

Cut-off SpO2 (%) Sensitivity (95% CI) Specificity (95% CI) 80 ≤ 90 0.39 (0.30-0.49) 0.98 (0.91-1.00) ≤ 91 0.47 (0.37-0.57) 0.98 (0.91-1.00) 60 ≤ 92 0.53 (0.43-0.63) 0.97 (0.88-1.00) ≤ 93 0.63 (0.53-0.72) 0.97 (0.88-1.00) 40 ≤ 94 0.75 (0.65-0.83) 0.97 (0.88-1.00) Sensitivity (%) ≤ 95 0.82 (0.74-0.89) 0.95 (0.86-0.99) ≤ 96 0.84 (0.76-0.91) 0.84 (0.73-0.93) 20 ≤ 97 0.90 (0.83-0.95) 0.66 (0.52-0.78)

0 020406080 100 100% – Specificity (%) – Figure 3 Receiver-operating characteristic (ROC) curve evaluating the diagnostic value of SpO2 as a diagnostic test of pulmonary edema according to < fi # ¼ LUS (area under the curve, 0.893; 95% CI, 0.838-0.948; P .0001). Coordinates of the ROC curve identi ed an optimal cutoff value of 95%. SpO2 peripheral oxygen saturation. See Figure 1 legend for expansion of other abbreviations.

chestjournal.org 1591 Acute onset of cough and/or dyspnea during or immediately after Vansbrosimningen in 2018-2019

SpO2 < 95% SpO2 > 95% (n = 87) (n = 73)

Crackles (+) Crackles (–) Crackles (+) Crackles (–) (n = 76) (n = 11) (n = 20) (n = 53)

S/H (+) S/H (–) S/H (+) S/H (–) S/H (+) S/H (–) S/H (+) S/H (–) (n = 28) (n = 48) (n = 2) (n = 9) (n = 3) (n = 17) (n = 6) (n = 47)

LUS (+) n = 28 LUS (+) n = 47 LUS (+) n = 2 LUS (+) n = 7 LUS (+) n = 3 LUS (+) n = 12 LUS (+) n = 0 LUS (+) n = 3 LUS (–) n = 0 LUS (–) n = 1 LUS (–) n = 0 LUS (–) n = 2 LUS (–) n = 0 LUS (–) n = 5 LUS (–) n = 6 LUS (–) n = 44

Figure 4 – Tree diagram presenting clinical findings in patients with acute onset of cough and/or dyspnea during or immediately following Vans- # > fi brosimningen in 2018 and 2019. Patients sorted stepwise based on SpO2 95% or 95%, lung auscultation ndings of crackles, and reported symptoms of excessive S/H. Number of LUS (þ) and LUS (–) patients are presented for each group. S/H ¼ sputum and/or hemoptysis. See Figure 1 and 2 legends for expansion of abbreviations. treatment of the patient will be determined according to checkpoints for SIPE. In our study, adding findings of the severity of symptoms and the clinical condition of rhonchi lowered the specificity and positive predictive the patient. value of LUS-verified SIPE. In patients presenting with rhonchi, LUS can be a valuable diagnostic tool to Correlation between SpO and LUS-verified pulmonary 2 differentiate between asthma and pulmonary edema. edema has been described in high-altitude edema.23 Cold- or exercise-induced asthma and pulmonary “Checkpoint” levels of 90% and 92% for clinical edema may also coexist in these patients. diagnosis of SIPE have previously been suggested.6,10 Based on our data, choosing a cutoff level below Compared with previous reports, the frequency of 95% will result in a loss of sensitivity for SIPE diagnosis. hemoptysis in this study was low, and no patient was fi 6,9 The reliability of SpO2 and auscultation ndings in cold, disoriented. This might be explained by early wet, and exhausted swimmers was a major concern. interruption of swimming activity. At However, reference individuals, who swam the same Vansbrosimningen, first aid personnel along the distances but who had no respiratory symptoms, riverside identify swimmers with respiratory symptoms exhibited SpO2 values of 98% on average, had normal and advise them to interrupt the race. Interruption of respiratory sounds, and did not show extravascular lung swimming has been suggested to define the severity of water on LUS. Crackles have previously been proposed SIPE; however, this criterion will for obvious reasons be as a diagnostic criterion of SIPE.4,9 Grunig et al6 also dubious in our context.4 Water aspiration has previously included auscultation of rales and wheezing as been suggested as an exclusion criterion for SIPE.4,6,9,10

TABLE 2 ] Multiple Logistic Regression Analysis of Diagnostic Criteria for the Outcome of Pulmonary Edema Based on LUS

Variable Parameter Estimate Adjusted OR 95% CI P Value Intercept –7.14

SpO2 # 95% 3.68 39.62 7.52-208.82 < .0001 Crackles 4.17 64.58 13.10-318.44 < .0001 Sputum/hemoptysis 0.59 1.81 0.27-11.87 .539

The regression model was adjusted by age. Overall percentage predicted by model, 94.4%. Nagelkerke R2 ¼ 0.84. SIPE ¼ swimming-induced pulmonary edema. See Table 1 legend for expansion of other abbreviations.

1592 Original Research [ 158#4 CHEST OCTOBER 2020 ] TABLE 3 ] Evaluation of Diagnostic Criteria for Pulmonary Edema based on LUS

LUS (þ) LUS (–) Sensitivity (%) Specificity (%) PPV (%) NPV (%) (n ¼ 102) (n ¼ 58) (95% CI) (95% CI) (95% CI) (95% CI) Clinical criteria Saturation

SpO2 # 95% 84 3 82 (75-90) 95 (89-100) 97 (93-100) 75 (65-85)

SpO2 > 95% 18 55 Auscultation Crackles 90 6 88 (82-94) 90 (82-97) 94 (89-99) 81 (72-91) No crackles 12 52 Symptoms Sputum and/or 33 6 32 (23-41) 90 (82-97) 85 (73-96) 43 (34-52) hemoptysis Cough and/or dyspnea 69 52 only Combination of clinical criteria

SpO2 # 95% or crackles Yes 99 8 97 (94-100) 86 (77-95) 93 (88-98) 94 (88-100) No 3 50

SpO2 # 95% and crackles Yes 75 1 74 (65-82) 98 (95-100) 99 (96-100) 68 (58-78) No 27 57

Criteria include SpO2 with a cut off of 95%, auscultation findings of crackles, and reported symptoms of sputum and/or hemoptysis. Suggested combination of clinical criteria for SIPE are also evaluated. NPV ¼ negative predictive value; PPV ¼ positive predictive value. See Table 1 and 2 legends for expansion of other abbreviations.

Acute onset of cough and/or dyspnea during or immediately after swimming in cold open water

SpO2 < 95% SpO2 > 95%

Crackles (+) Crackles (–) Crackles (+) Crackles (–)

S/H increase likelihood of SIPE

SIPE Suspected SIPE Suspected SIPE Non-SIPE Figure 5 – Suggested algorithm for SIPE diagnosis in patients with acute onset of cough and/or dyspnea during swimming in open LUS suggested for differential diagnostics water. The algorithm is based on SpO2 and crackles on lung auscultation, with excessive S/H supporting the diagnosis. Patients with fi # ndings of crackles and SpO2 95% could be Differential diagnostics diagnosed with SIPE based on clinical evalu- - Chest pain: consider acute coronary syndrome (ACS) ation. For patients with findings of crackles or # - Consider other potentiaI causes of respiratory symptoms based on SpO2 95%, LUS is suggested for differential clinical history e.g. asthma, respiratory infections, heart failure. diagnosis if available. SIPE ¼ swimming- These conditions can coexist with SIPE. induced pulmonary edema. See Figure 1, 2, - Water aspiration is not an exclusion criterion for SIPE and 3 legends for expansion of other abbreviations.

chestjournal.org 1593 We found an equal frequency of self-reported aspiration Novel Findings in Clinical Presentation of SIPE among patients with or without pulmonary edema Both auscultation findings and LUS edema were according to LUS. Our data suggest that at least minor predominantly located to the anterior chest. Similarly, in aspiration of water per se does not cause pulmonary a study of breath-hold divers, pulmonary edema was edema and does not exclude SIPE. Chest pain was detected over the anterior but not posterior chest.21 The uncommon among swimmers with SIPE. Because there anterior localization of the edema could be due to might be an overlap between SIPE and acute coronary dependent edema from swimming in the prone position. syndrome, all patients with chest pain should Our findings emphasize the importance of auscultation immediately be treated as having suspected acute of the anterior chest when SIPE is suspected. Eleven coronary syndrome. For patients with respiratory patients with symptoms of SIPE presented with fi distress lacking criteria for SIPE or without LUS-veri ed unilateral pulmonary edema, predominantly on the right edema, other diagnoses should be considered. side. There is no previous definition of unilateral LUS for Diagnosis of SIPE pulmonary edema based on LUS examination in the literature.19 Because this pattern was repeatedly noticed Point-of-care LUS has high diagnostic value in acute in the study cohort, unilateral edema was defined as two respiratory failure and provides a fast and mobile or more positive regions unilaterally. Although rare, 15,17 alternative to other radiologic assessments. LUS unilateral pulmonary edema has been described in high- corresponds well with the reference method, CT altitude pulmonary edema, usually affecting the right 16,18 scanning, and degree of extravascular lung water. lung and often caused by unilateral pulmonary artery fi Based on clinical ndings, it was reasonable that B-lines pathologies.29,30 Unilateral edema, in the dependent distributed both bilaterally or unilaterally represented lung, was reported in three combat swimmers, pulmonary edema in the current patients. B-line artifacts swimming in the lateral decubitus position.31 There are fi are not speci c for pulmonary edema but can represent anatomic differences between the right and left lung, fi other interstitial syndromes (eg, pulmonary brosis, resulting in more frequent aspirations in the right 19 pneumonia, atelectasis). We considered these bronchus, as well as less efficient lymphatic drainage of conditions, as well as acute pulmonary edema caused by the right lung.32 Individual variations of venous drainage acute heart failure and mitral valve prolapse, less likely from the right lung vein to the left atrium can also 24 in this otherwise healthy study population. Occasional predispose for right-sided unilateral pulmonary B-line artifacts, without underlying pathology, appear edema.33 Only four of the 11 patients reported 25,26 with increasing age. The widespread presentation of aspiration of water during swimming, and a majority B-lines in the current middle-aged population were swimming breaststroke, leaving us with no obvious strengthens the diagnosis of pulmonary edema caused explanation for these unilateral findings. by swimming. LUS identifies also small amounts of extravascular lung water, potentially reflecting mild or even asymptomatic stages of SIPE of less clinical Interpretation relevance.27 Subclinical increase in lung water has been We present diagnostic criteria, based on peripheral detected by LUS in asymptomatic ironman athletes and saturation and lung auscultation, to identify patients breath-hold divers, as well as in two of the reference with SIPE in a cohort of open water swimmers with subjects who had no respiratory symptoms.20,28 To note, acute respiratory symptoms. Novel findings of anterior our diagnostic algorithm was based only on patients and unilateral pulmonary edema contribute to a unique with acute respiratory symptoms. dataset of an underreported condition.

1594 Original Research [ 158#4 CHEST OCTOBER 2020 ] Acknowledgments 7. Cochard G, Arvieux J, Lacour JM, 21. Boussuges A, Coulange M, Bessereau J, Madouas G, Mongredien H, Arvieux CC. et al. Ultrasound lung comets induced by Author contributions: M. H. takes Pulmonary edema in scuba divers: repeated breath-hold diving, a study in responsibility for the content of the recurrence and fatal outcome. Undersea underwater fishermen. Scand J Med Sci manuscript, including data and analysis. M. Hyperb Med. 2005;32(1):39-44. Sports. 2011;21(6):e384-e392. H. and A. B. E. initiated the study. M. H. and 8. Hohmann E, Glatt V, Tetsworth K. C. S. performed the data analysis and wrote 22. Alonso JV, Chowdhury M, Borakati R, Swimming induced pulmonary oedema in Gankande U. Swimming-induced the first draft of the manuscript, with help athletes—a systematic review and best pulmonary oedema an uncommon from L. K. and C. K. All authors, including D. evidence synthesis. BMC Sports Sci Med condition diagnosed with POCUS L., took active part in study design, logistics, Rehabil. 2018;10:18. ultrasound. Am J Emerg Med. 2017;35(12): data collection and interpretation of the data. 1986.e3-1986.e4. All authors reviewed and approved the final 9. Adir Y, Shupak A, Gil A, et al. Swimming- induced pulmonary edema: clinical manuscript. 23. Yang W, Wang Y, Qiu Z, et al. Lung presentation and serial lung function. ultrasound is accurate for the diagnosis of Financial/nonfinancial disclosures: None Chest. 2004;126(2):394-399. high-altitude pulmonary edema: a declared. 10. Ludwig BB, Mahon RT, Schwartzman EL. prospective study. Can Respir J. 2018;2018:5804942. Role of sponsors: The funding sources had Cardiopulmonary function after recovery fl from swimming-induced pulmonary edema. 24. Wilmshurst PT. Immersion pulmonary no in uence on study design, data collection, Clin J Sport Med. 2006;16(4):348-351. or conclusions drawn from the dataset. oedema: a cardiological perspective. 11. Spencer S, Dickinson J, Forbes L. Diving Hyperb Med. 2019;49(1):30-40. Other contributions: The authors thank all Occurrence, risk factors, prognosis and 25. Chiesa AM, Ciccarese F, Gardelli G, et al. swimmers for their participation and health prevention of swimming-induced Sonography of the normal lung: personnel during Vansbrosimningen for help pulmonary oedema: a systematic review. comparison between young and elderly with data collection. A special Sports Med Open. 2018;4(1):43. subjects. J Clin Ultrasound. 2015;43(4): acknowledgment is given to Martin 12. Smith R, Ormerod JOM, Sabharwal N, 230-234. Annsberg, MD, Ida Döl, RN, Björn Kipps C. Swimming-induced pulmonary Pettersson, and Simon Mårdstam, MD, in the edema: current perspectives. Open Access J 26. 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