Recommendations for Lung Ultrasound in Internal Medicine

A growing amount of evidence prompts us to update the first version of recommendations for lung ultrasound in internal medicine (POLLUS-IM) that was published in 2018. The recommendations were established in several stages, consisting of: literature review, assessment of literature data quality (with the application of QUADAS, QUADAS-2 and GRADE criteria) and expert evaluation carried out consistently with the modified Delphi method (three rounds of on-line discussions, followed by a secret ballot by the panel of experts after each completed discussion). Publications to be analyzed were selected from the following databases: Pubmed, Medline, OVID, and Embase. New reports published as of October 2019 were added to the existing POLLUS-IM database used for the original publication of 2018. Altogether, 528 publications were systematically reviewed, including 253 new reports published between September 2017 and October 2019. The new recommendations concern the following conditions and issues: pneumonia, heart failure, monitoring dialyzed patients’ hydration status, assessment of pleural effusion, pulmonary embolism and diaphragm function assessment. POLLUS-IM 2020 recommendations were established primarily for clinicians who utilize lung ultrasound in their everyday clinical work.


Introduction
The progress that has occurred since the publication of the first recommendations for the use of lung ultrasound in internal medicine POLLUS-IM 2018 [1] prompts their update. The last systematic review of relevant literature was completed in August 2017, and 275 original papers were further analyzed. Between August 2017 and October 2019, 253 new original papers devoted to the use of lung ultrasound in adult patients not treated in Intensive Care Units were published. The need to update the recommendations correlates with the rapidly enlarging group of physicians who perform lung ultrasound (LUS) exams in their everyday clinical practice. The working group involved in the updating of the recommendations is a multidisciplinary team, consisting of 11 specialists in internal medicine, pulmonology, cardiology, geriatrics, radiology and pediatrics. Two specialists in lung ultrasound who supervised the updating process (GM and TT) were also involved. The working group was established based on participation application form and experience in lung ultrasound. New statements were formulated based on the available data that most frequently appeared in the selected publications. They concerned the following conditions and issues: pneumonia, pneumothorax, pulmonary embolism, heart failure, diagnosis of pleural effusion and of breathlessness, as well as an assessment of hyperhydration in patients receiving dialysis. The established statements first helped in further assessing the literature data's credibility, which was conducted by a six-person team. Subsequently, the statements were subjected to experts' opinions.
When analyzing the credibility of the literature data, the following parameters were taken into account: age, sex, number of examined patients, homogeneity of patient groups participating in the study, inclusion and exclusion criteria, publication type (prospective, retrospective, meta-analysis), sensitivity and specificity of the employed method, true positive (TP), false positive (FP), true negative (TN), false negative (FN) results, and the imaging method recognized as the gold diagnostic standard. Moreover, the Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS score and QUADAS score-2), recommended by the Cochrane Diagnostic Test Accuracy Working Group and GRADE (The Grading of Recommendations Assessment, Development and Evaluation), was employed to estimate the methodological quality of the works selected for analysis [2][3][4] ( Table  1).
The final opinion formulated by the experts was a result of a three-step procedure conducted via the Internet (online). It consisted of discussions among experts, was carried out according to the modified Delphi method, and involved three rounds of an anonymous ballots featuring the use of personalized passwords. The first round of voting took place on 10-12 January 2020. The statements considered as successfully voted through were those that received ≥ 80% of positive votes. More than 50% of votes against a given statement were considered as unequivocally negating the validity of that New statements were formulated based on the available data that most frequently appeared in the selected publications. They concerned the following conditions and issues: pneumonia, pneumothorax, pulmonary embolism, heart failure, diagnosis of pleural effusion and of breathlessness, as well as an assessment of hyperhydration in patients receiving dialysis. The established statements first helped in further assessing the literature data's credibility, which was conducted by a six-person team. Subsequently, the statements were subjected to experts' opinions.
When analyzing the credibility of the literature data, the following parameters were taken into account: age, sex, number of examined patients, homogeneity of patient groups participating in the study, inclusion and exclusion criteria, publication type (prospective, retrospective, meta-analysis), sensitivity and specificity of the employed method, true positive (TP), false positive (FP), true negative (TN), false negative (FN) results, and the imaging method recognized as the gold diagnostic standard. Moreover, the Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS score and QUADAS score-2), recommended by the Cochrane Diagnostic Test Accuracy Working Group and GRADE (The Grading of Recommendations Assessment, Development and Evaluation), was employed to estimate the methodological quality of the works selected for analysis [2][3][4] (Table 1). The final opinion formulated by the experts was a result of a three-step procedure conducted via the Internet (online). It consisted of discussions among experts, was carried out according to the modified Delphi method, and involved three rounds of an anonymous ballots featuring the use of personalized passwords. The first round of voting took place on 10-12 January 2020. The statements considered as successfully voted through were those that received ≥ 80% of positive votes. More than 50% of votes against a given statement were considered as unequivocally negating the validity of that statement. Statements that received between 50% and 80% of positive votes were discussed once more and underwent subsequent voting in the second round ( Table 2). The second round of voting was held on 16-18 January 2020. In this voting, a consensus was reached with respect to the ambiguous results from the first round. The third and final round of voting was organized on 23-25 January 2020; it concluded with unambiguous results and consensus as to the final recommendations (Tables 2 and 3). Table 2. Quality of evidence, GRADE.

Grade Interpretation
A High-data from multiple meta-analyses, and/or it is unlikely that further research will change the credibility of the effectiveness or accuracy of the method B Moderate-data from individual large non-randomized trials (meta-analysis, prospective cohort study), and/or further testing may have a significant impact on the credibility of the effectiveness or accuracy of the method C Low or very low-agreed expert opinion and/or data from small studies, retrospective studies, registers, case series, or case reports, and/or it is very likely that further testing will have an important impact on the credibility of effectiveness or accuracy of the method. Any estimation of the effects or accuracy of the method is very uncertain (very low) Table 3. Strength of recommendations and its practical implications.

Strength of Recommendation
Interpretation and Practical Implication of Recommendation

3.
In a patient with acute respiratory failure and with a significant suspicion of pneumothorax, it is not necessary to search for the lung point. (A1) 4.
Lung ultrasound is a superior diagnostic imaging technique to chest X-ray for patients with pneumothorax; however, lung ultrasound is less useful than chest X-ray for making therapeutic decisions, such as chest drainage. (A1) 5.

1.
Chest ultrasound is a more sensitive and more specific diagnostic imaging technique for pleural effusion than chest X-ray. (A1) 2.
The sensitivity of chest ultrasound, when determining the volume of pleural fluid, is similar to that of chest computed tomography. (B1) 3.
Chest ultrasound is a good method for chest imaging that allows for the finding of an optimal place to perform a puncture. (A1) 4.
Chest ultrasound allows for the minimization of post-puncture complications. (A1) 5.
Interstitial syndrome may be caused by various conditions, including cardiogenic pulmonary edema, non-cardiogenic pulmonary edema, interstitial lung disease, infections and prior bronchoalveolar lavage. (A1) 4.
Convex/micro-convex or sector transducers, and, in some cases, a linear transducer, are recommended for the differential diagnosis of the causes of interstitial syndrome. (A1) Experts' comments [42,43] (a) B-line artifacts are laser-like vertical reverberation artifacts arising from the pleural line, extending to the bottom of the screen, and moving along with the movements of the pleural line. The definition of a B-line artifact is based on the use of convex/micro-convex transducers. (b) The lung sliding sign may be limited or absent in the case of prior pleurodesis or the so-called stiff lung. (c) A linear transducer is recommended for the differential diagnosis of the causes of "interstitial syndrome". This is particularly important in the case of bilateral asymmetric interstitial lesions, in the presence of the so-called spared areas, and also in the case of suspected respiratory tract infections, as well as in any clinically ambiguous cause of interstitial pulmonary lesions.
Cardiogenic Pulmonary Edema and Heart Failure 1.
The sonographic features of cardiogenic pulmonary edema are as follows: most frequently bilateral, gravitational and symmetrical interstitial syndrome, and/or alveolar-interstitial syndrome and/or the white lung sign. (A1) 2.
Lung ultrasound is a good diagnostic strategy for diagnosing cardiogenic pulmonary edema. (A1) 3.
The use of lung ultrasound in patients diagnosed with heart failure is an important monitoring method during periods of clinical stabilization and exacerbation. (A1) 4.
Lung ultrasound performed for patients diagnosed with heart failure allows for the identification of patients at high risk of hospitalization and mortality. (A1) 5.
In patients with heart failure, an increased number of B-lines is a predictor of serious cardiovascular events in the near future. (A1) 6.
The number of B-lines is a predictor of and correlates with the risk of adverse cardiovascular events, re-hospitalization and mortality for patients with heart failure. (A1) 7.
The 11. An ultrasound image of the lungs of patients with heart failure is useful when deciding on the intensity of diuretic therapy. (A1) 12. In a patient with dyspnea, the absence of B-line artifacts in lung ultrasound excludes the diagnosis of cardiogenic pulmonary edema, and indicates the necessity of searching for other causes of dyspnea. (B1) 13. Lung ultrasound is a good and accurate method differentiating cardiogenic and pulmonary causes of dyspnea. (A1) 14. Lung ultrasound is a superior technique to chest X-ray for imaging cardiogenic pulmonary edema, and is comparable to that of chest computed tomography. (A1) 15. Lung ultrasound is complementary to echocardiography in a clinical assessment of clinically manifested and occult heart failure. (A1) Experts' comments  (a) Interstitial syndrome, alveolar-interstitial syndrome and the white lung sign define successively occurring more advanced stages of interstitial lesions in the course of cardiogenic pulmonary edema. All three of these signs require that at least three B-line artifacts be found in one intercostal space in a single longitudinal scan plane (in relation to the body axis); however, the distance between individual B-line artifacts decreases with an increasing fluid volume in the interstitial space and in the alveoli. The use of lung ultrasound may be a superior diagnostic strategy to chest X-ray for diagnosing interstitial lung disease involving pulmonary fibrosis. (A1) 3.
The use of lung ultrasound in the monitoring of interstitial lung disease involving pulmonary fibrosis may be helpful (C1) Experts' comments [1,42,43,132,133] (a) Pleural line abnormalities found in patients with pulmonary fibrosis are described as irregular, coarse in appearance, fragmented or blurred. (b) The use of lung ultrasound in the diagnosis of interstitial pulmonary disease in the active phase is based on case reports, and refers to pulmonary vasculitis, sarcoidosis, hypersensitivity pneumonitis, diffuse alveolar hemorrhage secondary to systemic connective tissue diseases, pulmonary alveolar proteinosis, and interstitial pneumonia secondary to systemic connective tissue diseases.

1.
The sonographic features of consolidations are as follows: a subpleural hypoechoic area with a liver-like structure. (A1) 2.
The use of lung ultrasound may be a superior diagnostic strategy to chest X-ray for confirming the presence of subpleural consolidations. (A1) 3.
Subpleural consolidations may have various underlying causes, most commonly pneumonia, atelectasis (compression-or resorption-related), pulmonary embolism, subpleural neoplastic lesions (primary or metastatic), and lung contusion. (A1) Experts' comments [1,134,135] Diagnostics 2020, 10, 597 9 of 25 (a) Experts emphasize the coexistence of multiple morbidities within the respiratory system. The coexistence of more than one respiratory system disease, found in clinical practice, results in the overlapping of several abnormalities in the lung ultrasound scan. It should also be remembered that computed tomography performed according to a protocol suitable for an initial diagnosis is the reference examination in the assessment of pulmonary lesions. The use of lung ultrasound may be a superior diagnostic strategy to chest X-ray for confirming the presence of pneumonia. (A1) 3.
When pneumonia is clinically suspected, the detection of typical inflammatory consolidations in lung ultrasound does not require further confirmation with chest X-ray. (A1) 4.
Lung ultrasound is more sensitive and more specific in the diagnosis of community-acquired pneumonia than chest X-ray, and is comparable to the effectiveness of chest computed tomography. (A1) 5.

(d) A dynamic air bronchogram is visible on inspiration and disappears on expiration. (e) A normal vascular pattern is one that is consistent with the anatomical standard-it is visible
with the use of CD and/or PD options. (f) Experts emphasize that inflammatory lesions caused by tuberculosis, systemic mycosis, pneumocystosis, viral infection and pneumonia of an atypical etiology may present a different sonomorphology than the one described above. It should also be remembered that typical inflammatory lesions may overlap with those caused by less common pathogens. (g) The diagnostic sensitivity of lung ultrasound for the diagnosis of pneumonia amounts to 87-95%, and specificity to 80-96%. The interpretation of the examination results must account for clinical data. The significance of lung ultrasound results for diagnostic and therapeutic procedures may be particularly important in the following patient groups: geriatric patients, chronically immobile bedridden patients, and patients with chest deformities. 3.
The use of lung ultrasound may be a superior diagnostic strategy to chest X-ray for confirming compression atelectasis. (A1) 4.
The use of lung ultrasound may be a superior diagnostic strategy to chest X-ray for confirming resorption atelectasis. (A1) Experts' comments [154,155] (a) Blood flow in CD and PD options is normal only within the area of compression atelectasis, or within the consolidation area constituting resorption atelectasis and not being a pathological mass associated with cancer. (b) A static air bronchogram represents the presence of air in the bronchial tree and is visible during all respiration phases.
Pulmonary Embolism

1.
The sonographic features of pulmonary embolism may be as follows: consolidation, mostly wedge-shaped or oval/rounded, centrally located echo, flow amputation in the CD option (the so-called vascular sign), local fluid immediately above the subpleural lesion, and local interstitial lesions. (A1) 2.
If pulmonary embolism is suspected, lung ultrasound may be a good diagnostic strategy to confirm the diagnosis. (A1) 3.
If pulmonary embolism is suspected (according to the Wells score), the combination of lung ultrasound, transthoracic echocardiography (ECHO) and compression ultrasound (CUS) venous imaging significantly increases the sensitivity and specificity of pulmonary embolism diagnosis, and consequently allows for limiting the number of angio-CT exams performed. (A1) 4.
The diagnosis of pulmonary embolism is likely if one abnormality typical of pulmonary embolism is detected in lung ultrasound. (C1) 6.
The absence of abnormalities typical of pulmonary embolism does not rule out its diagnosis. (A1) Experts' comments [156][157][158][159][160][161][162][163][164][165][166] (a) In the case of patients with acute respiratory failure and a high risk of death, it is recommended to follow the BLUE protocol and criteria for the diagnosis of pulmonary embolism designed therein as a potential cause of the patient's acute status. (b) Lung ultrasound may be an alternative technique for the diagnosis of pulmonary embolism when angio-CT cannot be performed or is contraindicated, e.g., in pregnant women, patients with acute kidney failure, and patients allergic to contrast agents. (c) The use of lung ultrasound in the diagnosis of pulmonary embolism may increase the sensitivity and specificity of commonly applied assessment scores for the clinical risk of embolism (e.g., the Wells score); it does not, however, apply to the assessment of the patient's prognosis. The use of lung ultrasound is a good diagnostic strategy during invasive procedures (transthoracic biopsy) in the diagnosis of subpleural lesions suspected of being malignant. (A1)

3.
Lung ultrasound is a good imaging technique that allows for the localization of peripheral pulmonary tumors adjacent to the chest wall, or tumors within the consolidation area below the fluid in the pleural cavity. (B1) Experts' comments [1,167,168] (a) Subpleural malignant lesions may be accompanied by accessory vascularization originating from intercostal vessels that can be visualized in CD and PD options. (b) The use of ultrasound guidance during a biopsy is applicable for both subpleural lesions and biopsies through the acoustic window formed by fluid or atelectasis.

Diaphragm
The ultrasound assessment of diaphragm function in patients with chronic obstructive pulmonary disease (COPD) may prove useful when predicting therapeutic effectiveness (e.g., non-invasive ventilation (NIV)). (C1) Experts' comment [169][170][171][172][173][174] Ultrasonography can assess the characteristics of diaphragmatic movement, such as amplitude, force and velocity of contraction, special patterns of motion, and changes in diaphragmatic thickness during inspiration.

1.
The use of lung ultrasound may be a good diagnostic strategy for determining the causes of dyspnea. (A1) 2.
The use of lung ultrasound may be a good diagnostic strategy for the differential diagnosis of pleuritic chest pain. (A1) 3.
The use of lung ultrasound may be a good screening strategy for the differential diagnosis of acute cough (A1) 4.
A lung ultrasound examination performed by a trained clinician is at a comparable level to a lung ultrasound examination performed by a radiologist. (A1) Experts' comments [1,120,158,175,176] Publications clearly indicate that a bedside lung ultrasound examination performed by trained clinicians is a better solution than transporting the patient to a radiology unit to perform lung ultrasound there. The clinician has data from the patient's medical history and physical examination, as well as knowledge as to the patient's present status, which all impact on the accuracy of the final diagnosis. The technique of performing a lung ultrasound examination for internal medicine patients is presented in Figure 2.
Diagnostics 2020, 10, x FOR PEER REVIEW 11 of 25 (b) The use of ultrasound guidance during a biopsy is applicable for both subpleural lesions and biopsies through the acoustic window formed by fluid or atelectasis.

Diaphragm
The ultrasound assessment of diaphragm function in patients with chronic obstructive pulmonary disease (COPD) may prove useful when predicting therapeutic effectiveness (e.g., noninvasive ventilation (NIV)). (C1) Experts' comment [170][171][172][173][174][175] Ultrasonography can assess the characteristics of diaphragmatic movement, such as amplitude, force and velocity of contraction, special patterns of motion, and changes in diaphragmatic thickness during inspiration.

Other Indications
1. The use of lung ultrasound may be a good diagnostic strategy for determining the causes of dyspnea. (A1) 2. The use of lung ultrasound may be a good diagnostic strategy for the differential diagnosis of pleuritic chest pain. (A1) 3. The use of lung ultrasound may be a good screening strategy for the differential diagnosis of acute cough (A1) 4. A lung ultrasound examination performed by a trained clinician is at a comparable level to a lung ultrasound examination performed by a radiologist. (A1) Experts' comments [1,120,159,[176][177] Publications clearly indicate that a bedside lung ultrasound examination performed by trained clinicians is a better solution than transporting the patient to a radiology unit to perform lung ultrasound there. The clinician has data from the patient's medical history and physical examination, as well as knowledge as to the patient's present status, which all impact on the accuracy of the final diagnosis. The technique of performing a lung ultrasound examination for internal medicine patients is presented in Figure 2.

1
Bedside examination is recommended for a clinically unstable patient with dyspnea. 2 The lung ultrasound scanning technique depends on the patient's clinical status and should

1.
Bedside examination is recommended for a clinically unstable patient with dyspnea.

2.
The lung ultrasound scanning technique depends on the patient's clinical status and should cover the largest possible area of the lungs.

3.
Lung ultrasound performed by a trained clinician for a patient with respiratory failure is a good and safe diagnostic constituent for the differential diagnosis of pulmonary diseases.

4.
Basic training in the theoretical aspects and practical use of lung ultrasound is recommended for physicians during their specialty training programs, including internal medicine, cardiology, pulmonology and nephrology. 5.
The recommended basic course for clinicians during their specialty training programs should cover the diagnosis of pleural effusion, pneumothorax, cardiogenic and non-cardiogenic pulmonary edema, interstitial lung disease involving fibrosis, pneumonia, atelectasis, pulmonary embolism, subpleural malignant lesions, rib fracture as well as assistance during invasive diagnostic procedures and therapies. 6.
It is recommended to incorporate basic lung ultrasound training into the curriculum of students at faculties of medicine in medical universities.
Experts' comment Convex (or possibly micro-convex or sector) and linear transducers are recommended when examining a patient in a stable clinical condition. The patient can be examined in a sitting position or a lying position (except for patients in a forced position or with orthopnea, for whom the examination is performed in a sitting or semi-sitting position).

Practical Aspects of Lung Ultrasound Examination
There are many proposed protocols for lung ultrasound in the literature. Some are dedicated to the quick assessment of a patient with acute dyspnea (e.g., BLUE protocol), while others are used in the semi-quantitative assessment of pulmonary congestion in patients with heart failure (protocol 28 scans, also used in haemodialysis patients, or its modifications). The authors of this document propose to follow the following general principles of examination:

1.
When examining the patient, the protocol appropriate to the clinical situation should be selected each time; 2.
If the patient's condition allows it, assess the anterior, lateral and posterior surfaces of the chest in the vertical and supine positions of the patient, using a convex probe and then a linear probe ( Figure 2); 3.
When analyzing the obtained ultrasound image, first of all, answer the following questions:

Conclusions
Large amounts of data from scientific publications confirm our belief that lung ultrasound as a lung imaging technique is presently an important diagnostic tool in the everyday clinical practice of specialists in internal medicine and related specialties. The experiences of clinicians gathered during the last two years has provided new data allowing for the reaching of a consensus related to diagnostic issues in, among others, patients with heart failure and pneumonia, and patients receiving dialysis. Lung ultrasound facilitates a rapid and efficient diagnosis or suspicion of specific pulmonary diseases. Consequently, the utilization of lung ultrasound expedites decisions regarding the introduction of an appropriate therapy, or the extension of the diagnostic process as compared to the classical diagnostic procedures. These recommendations will be updated along with the accumulation of new, reliable reports in medical literature.

Conclusions
Large amounts of data from scientific publications confirm our belief that lung ultrasound as a lung imaging technique is presently an important diagnostic tool in the everyday clinical practice of specialists in internal medicine and related specialties. The experiences of clinicians gathered during the last two years has provided new data allowing for the reaching of a consensus related to diagnostic issues in, among others, patients with heart failure and pneumonia, and patients receiving dialysis. Lung ultrasound facilitates a rapid and efficient diagnosis or suspicion of specific pulmonary diseases. Consequently, the utilization of lung ultrasound expedites decisions regarding the introduction of an appropriate therapy, or the extension of the diagnostic process as compared to the classical diagnostic procedures. These recommendations will be updated along with the accumulation of new, reliable reports in medical literature.