Exploring the link between a novel approach for computer aided lung sound analysis and imaging biomarkers: a cross-sectional study.

BACKGROUND: Computer Aided Lung Sound Analysis (CALSA) aims to overcome limitations associated with standard lung auscultation by removing the subjective component and allowing quantification of sound characteristics. In this proof-of-concept study, a novel automated approach was evaluated in real patient data by comparing lung sound characteristics to structural and functional imaging biomarkers. METHODS: Patients with cystic fibrosis (CF) aged > 5y were recruited in a prospective cross-sectional study. CT scans were analyzed by the CF-CT scoring method and Functional Respiratory Imaging (FRI). A digital stethoscope was used to record lung sounds at six chest locations. Following sound characteristics were determined: expiration-to-inspiration (E/I) signal power ratios within different frequency ranges, number of crackles per respiratory phase and wheeze parameters. Linear mixed-effects models were computed to relate CALSA parameters to imaging biomarkers on a lobar level. RESULTS: 222 recordings from 25 CF patients were included. Significant associations were found between E/I ratios and structural abnormalities, of which the ratio between 200 and 400 Hz appeared to be most clinically relevant due to its relation with bronchiectasis, mucus plugging, bronchial wall thickening and air trapping on CT. The number of crackles was also associated with multiple structural abnormalities as well as regional airway resistance determined by FRI. Wheeze parameters were not considered in the statistical analysis, since wheezing was detected in only one recording. CONCLUSIONS: The present study is the first to investigate associations between auscultatory findings and imaging biomarkers, which are considered the gold standard to evaluate the respiratory system. Despite the exploratory nature of this study, the results showed various meaningful associations that highlight the potential value of automated CALSA as a novel non-invasive outcome measure in future research and clinical practice.

The effect of posture on airflow distribution, airway geometry and air velocity in healthy subjects.

BACKGROUND: Gravity, and thus body position, can affect the regional distribution of lung ventilation and blood flow. Therefore, body positioning is a potential tool to improve regional ventilation, thereby possibly enhancing the effect of respiratory physiotherapy interventions. In this proof-of-concept study, functional respiratory imaging (FRI) was used to objectively assess effects of body position on regional airflow distribution in the lungs. METHODS: Five healthy volunteers were recruited. The participants were asked during FRI first to lie in supine position, afterwards in standardized right lateral position. RESULTS: In right lateral position there was significantly more regional ventilation also described as Imaging Airflow Distribution in the right lung than in the left lung (P < 0.001). Air velocity was significantly higher in the left lung (P < 0.05). In right lateral position there was significantly more airflow distribution in the right lung than in the left lung (P < 0.001). Significant changes were observed in airway geometry resulting in a decrease in imaged airway volume (P = 0.024) and a higher imaged airway resistance (P = 0.029) in the dependent lung. In general, the effect of right lateral position caused a significant increase in regional ventilation (P < 0.001) in the dependent lung when compared with the supine position. CONCLUSIONS: Changing body position leads to significant changes in regional lung ventilation, objectively assessed by FRI The volume based on the imaging parameters in the dependent lung is smaller in the lateral position than in the supine position. In right lateral decubitus position, airflow distribution is greater in dependent lung compared to the nondependent lung. TRIAL REGISTRATION: The trial has been submitted to www. CLINICALTRIALS: gov with identification number NCT01893697 on 07/02/2013.

Functional respiratory imaging provides novel insights into the long-term respiratory sequelae of bronchopulmonary dysplasia.

RATIONALE: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Lung function and imaging are classically used to assess BPD. Functional respiratory imaging (FRI) combines a structural and functional assessment of the airways and their vasculature. We aimed to assess BPD using FRI and to correlate these findings with the clinical presentation. METHODS: We included 37 adolescents with a history of preterm birth (22 BPD cases and 15 preterm controls). The study protocol included a detailed history, lung function testing and computed tomography (CT) (at total lung capacity (TLC) and functional residual capacity (FRC)) with FRI. CT images were also assessed using the Aukland scoring system. RESULTS: BPD patients had lower forced expiratory volume in 1 s to forced vital capacity ratio (p=0.02) and impaired diffusion capacity (p=0.02). Aukland CT scores were not different between the two groups. FRI analysis showed higher lobar volumes in BPD patients at FRC (p<0.01), but not at TLC. Airway resistance was significantly higher in the BPD group, especially in the distal airways. Additionally, FRI showed more air trapping in BPD patients, in contrast to findings on conventional CT images. CONCLUSION: This study is the first to use FRI in research for BPD. FRI analysis showed higher lobar volumes in BPD patients, indicating air trapping and reduced inspiratory capacity. In contrast to Aukland CT scores, FRI showed more air trapping in the BPD group, suggesting that FRI might be a more sensitive detection method. Importantly, we also showed increased distal airway resistance in BPD patients. By combining structural and functional assessment, FRI may help to better understand the long-term sequelae of BPD.

Body composition monitoring in children and adolescents: reproducibility and reference values.

There is an increasing need for suitable tools to evaluate body composition in paediatrics. The Body Composition Monitor (BCM) shows promise as a method, but reference values in children are lacking. Twenty children were included and measured twice by 4 different raters to asses inter- and intra-rater reproducibility of the BCM. Reliability was assessed using the Bland-Altman method and by calculating intraclass correlation coefficients (ICCs). The intra-rater ICCs were high (≥ 0.97) for all parameters measured by BCM as were the inter-rater ICCs for all parameters (≥ 0.98) except for overhydration (0.76). Consequently, a study was set up in which BCM measurements were performed in 2058 healthy children aged 3-18.5 years. The age- and gender-specific percentile values and reference curves for body composition (BMI, waist circumference, fat mass and lean tissue mass) and fluid status (extracellular and intracellular water and total body water) relative to age were produced using the GAMLSS method for growth curves.Conclusion: A high reproducibility of BCM measurements was found for fat mass, lean tissue mass, extracellular water and total body water. Reference values for these BCM parameters were calculated in over 2000 children and adolescents aged 3 to 18 years. What is Known • The 4-compartment model is regarded as the 'gold standard' of body composition methods, but is inappropriate for regular follow-up or screening of large groups, because of associated limitations. • Body Composition Monitor® is an inexpensive field method that has the potential to be an adequate monitoring tool. What is New • Good reproducibility of BCM measurements in children provides evidence to use the device in longitudinal follow-up, multicentre and comparative studies. • Paediatric reference values relative to age and sex for the various compartments of the body are provided.

Functional respiratory imaging in relation to classical outcome measures in cystic fibrosis: a cross-sectional study.

BACKGROUND: Functional Respiratory Imaging (FRI) combines HRCT scans with computational fluid dynamics to provide objective and quantitative information about lung structure and function. FRI has proven its value in pulmonary diseases such as COPD and asthma, but limited studies have focused on cystic fibrosis (CF). This study aims to investigate the relation of multiple FRI parameters to validated imaging parameters and classical respiratory outcomes in a CF population. METHODS: CF patients aged > 5 years scheduled for a chest CT were recruited in a cross-sectional study. FRI outcomes included regional airway volume, airway wall volume, airway resistance, lobar volume, air trapping and pulmonary blood distribution. Besides FRI, CT scans were independently evaluated by 2 readers using the CF-CT score. Spirometry and the 6-Minute Walk Test (6MWT) were also performed. Statistical tests included linear mixed-effects models, repeated measures correlations, Pearson and Spearman correlations. RESULTS: 39 CT scans of 24 (17M/7F) subjects were analyzed. Patients were 24 ± 9 years old and had a ppFEV1 of 71 ± 25% at the time of the first CT. All FRI parameters showed significant low-to-moderate correlations with the total CF-CT score, except for lobar volume. When considering the relation between FRI parameters and similar CF-CT subscores, significant correlations were found between parameters related to airway volume, air trapping and airway wall thickening. Air trapping, lobar volume after normal expiration and pulmonary blood distribution showed significant associations with all spirometric parameters and oxygen saturation at the end of 6MWT. In addition, air trapping was the only parameter related to the distance covered during 6MWT. A subgroup analysis showed considerably higher correlations in patients with mild lung disease (ppFEV1 ≥ 70%) compared to patients with moderate to severe lung disease (ppFEV1 < 70%) when comparing FRI to CF-CT scores. CONCLUSIONS: Multiple structural characteristics determined by FRI were associated with abnormalities determined by CF-CT score. Air trapping and pulmonary blood distribution appeared to be the most clinically relevant FRI parameters for CF patients due to their associations with classical outcome measures. The FRI methodology could particularly be of interest for patients with mild lung disease, although this should be confirmed in future research.

Outcome measures for airway clearance techniques in children with chronic obstructive lung diseases: a systematic review.

BACKGROUND: Airway clearance techniques (ACTs) are an important aspect of the treatment of children with chronic obstructive lung diseases. Unfortunately, a sound evidence base is lacking and airway clearance strategies are largely based on clinical expertise. One of the reasons for the limited evidence is the lack of appropriate outcome measures specifically related to the effectiveness of ACTs. This review discusses all outcome measures applied in previous research in the pediatric population to provide a baseline for future studies. DATA SOURCES: A systematic literature search was performed in PubMed, Web of Science and EMBASE databases. Search terms included chronic obstructive lung diseases and ACTs. STUDY SELECTION: Studies were independently selected by the investigators according to the eligibility criteria. After screening, 49 articles remained for further analysis. RESULTS AND CONCLUSIONS: Data are summarized according to the type of outcome measure. 48 (98%) studies performed pulmonary function tests, 19 (39%) assessed expectorated sputum, 10 (20%) parameters related to disease exacerbation, 8 (16%) oxygenation, 8 (16%) patient-reported outcomes, 5 (10%) exercise capacity and 5 (10%) applied imaging techniques. The synthesis of results showed a high discrepancy between studies due to differences in study design, population and the application of techniques. Since no 'gold standard' method could be identified, a combination of different outcome measures is recommended to gain a better understanding and to identify the potential effects of ACTs. An overview of important considerations has been provided to assist researchers in their choice of outcomes in future studies.

Personalized pulmonary rehabilitation program for patients with post-acute sequelae of COVID-19: A proof-of-concept retrospective study.

Long-COVID patients present with a decline in physical fitness. The aim of this study is to reveal the impact of pulmonary rehabilitation (PR) on physical fitness, quality of life (QoL), and parameters of quantified thorax CT. Long-COVID patients enrolled in a 3-month PR program were retrospectively studied. PR included endurance and resistance training three times a week. Assessments pre- and post-rehabilitation included quantified chest CT, pulmonary function tests (PFT), six-minute walk test (6MWT), cardiopulmonary exercise test, and questionnaires: Hospital Anxiety and Depression Scale, post-COVID-19 Functional Status scale, Borg score, and EuroQol. Seventeen subjects (5M/12F), mean age 42 ± 13 years, were included. PR improved all questionnaires' results significantly. Only significant difference in PFT parameters was correlation between baseline total lung capacity (TLC) and difference in TLC pre- and post-rehabilitation (p = 0.002). 6MWT increased from 329 to 365 m (p < 0.001), VO2max changed from 21 to 24 mL/kg/min (p = 0.007), peak load increased from 116 to 141 Watt (p < 0.001). Blood volume in small pulmonary vessels of 1.25 to 5 mm2 in cross-sectional area (BV5%) was higher than observed in patients with acute COVID-19 infection. After rehabilitation, BV5% decreased from 65% to 62% (p = 0.020). These changes correlated directly with changes in TLC (p = 0.039). Quantified CT airway volume increased after rehabilitation (p = 0.013). After rehabilitation, TLC tended to normalize due to (re)opening of small airways, with decline in air trapping and recruitment of alveoli. Furthermore, this study revealed that pulmonary rehabilitation can improve QoL and physical fitness in long-COVID patients.

Unraveling pathophysiologic mechanisms contributing to symptoms in patients with post-acute sequelae of COVID-19 (PASC): A retrospective study.

Patients with post-acute sequelae of COVID-19 (PASC) present with a decrease in physical fitness. The aim of this paper is to reveal the relations between the remaining symptoms, blood volume distribution, exercise tolerance, static and dynamic lung volumes, and overall functioning. Patients with PASC were retrospectively studied. Pulmonary function tests (PFT), 6-minute walk test (6MWT), and cardiopulmonary exercise test were performed. Chest CT was taken and quantified. Patients were divided into two groups: minor functional limitations (MFL) and severe functional limitations (SFL) based on the completed Post-COVID-19 Functional Status scale (PCFS). Twenty one patients (3 M; 18 FM), mean age 44 (IQR 21) were studied. Eighteen completed the PCFS (8 MFL; 10 SFL). VO2 max was suboptimal in both groups (not significant). 6MWT was significantly higher in MFL-group (p = 0.043). Subjects with SFL, had significant lower TLC (p = 0.029). The MFL-group had more air trapping (p = 0.036). Throughout the sample, air trapping correlated significantly with residual volume (RV) in L (p < 0.001). An increase in air trapping was related to an increase in BV5 (p < 0.001). Mean BV5 was 65% (IQR 5%). BV5% in patients with PASC was higher than in patients with acute COVID-19 infection. This increase in BV5% in patients with PASC is thought to be driven by the air trapping in the lobes. This study reveals that symptoms are more driven by occlusion of the small airways. Patients with more physical complaints have significantly lower TLC. All subjects encounter physical limitations as indicated by suboptimal VO2 max. Treatment should focus on opening or re-opening of small airways by recruiting alveoli.

Comprehensive Analysis System for Automated Respiratory Cycle Segmentation and Crackle Peak Detection.

Digital auscultation is a well-known method for assessing lung sounds, but remains a subjective process in typical practice, relying on the human interpretation. Several methods have been presented for detecting or analyzing crackles but are limited in their real-world application because few have been integrated into comprehensive systems or validated on non-ideal data. This work details a complete signal analysis methodology for analyzing crackles in challenging recordings. The procedure comprises five sequential processing blocks: (1) motion artifact detection, (2) deep learning denoising network, (3) respiratory cycle segmentation, (4) separation of discontinuous adventitious sounds from vesicular sounds, and (5) crackle peak detection. This system uses a collection of new methods and robustness-focused improvements on previous methods to analyze respiratory cycles and crackles therein. To validate the accuracy, the system is tested on a database of 1000 simulated lung sounds with varying levels of motion artifacts, ambient noise, cycle lengths and crackle intensities, in which ground truths are exactly known. The system performs with average F-score of 91.07% for detecting motion artifacts and 94.43% for respiratory cycle extraction, and an overall F-score of 94.08% for detecting the locations of individual crackles. The process also successfully detects healthy recordings. Preliminary validation is also presented on a small set of 20 patient recordings, for which the system performs comparably. These methods provide quantifiable analysis of respiratory sounds to enable clinicians to distinguish between types of crackles, their timing within the respiratory cycle, and the level of occurrence. Crackles are one of the most common abnormal lung sounds, presenting in multiple cardiorespiratory diseases. These features will contribute to a better understanding of disease severity and progression in an objective, simple and non-invasive way.

The short-term effects of ORKAMBI (lumacaftor/ivacaftor) on regional and distal lung structures using functional respiratory imaging.

BACKGROUND: Lumacaftor/ivacaftor (LUM/IVA) has shown modest benefits in previous research, but the exact effects in the cystic fibrosis (CF) lung remain unclear. This study aims to offer novel information on the mode of action of the cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drug by assessing lung structure and function using functional respiratory imaging (FRI). METHODS: CF patients aged ⩾12 years homozygous for F508del were recruited in an open-label study. Before and after 12 weeks of treatment with LUM/IVA, FRI was used to visualize regional information, such as air trapping, lobar volume and airway wall volume. Secondary outcomes included the CF-CT scoring system, spirometry, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) questionnaire, exercise tolerance and nutritional status. RESULTS: Of the 12 patients enrolled in the study, 11 completed all study visits. Concerning the FRI parameters, hyperinflation of the lung decreased, indicated by a reduction in air trapping and lobar volume at expiration. Also, a decrease in airway wall volume and a redistribution of pulmonary blood volume were noted, which might be related to a decrease in mucus impaction. Airway resistance, airway volume, internal airflow distribution and aerosol deposition pattern did not show significant changes. No significant improvements were found in any of the CF-CT scores or in the spirometric parameters. Other secondary outcomes showed similar results compared with previous research. Correlations at baseline were found between FRI and conventional outcomes, including physical functioning, spirometry and CF-CT scores. CONCLUSIONS: LUM/IVA decreased lung hyperinflation in combination with a potential decrease in mucus impaction, which can be related to an improved mucociliary transport. These results indicate that several FRI parameters, reflecting regional and distal lung structures, are more sensitive to changes caused by LUM/IVA than conventional respiratory outcomes.

The effect of intrapulmonary percussive ventilation in pediatric patients: A systematic review.

BACKGROUND: Intrapulmonary percussive ventilation (IPV) is frequently used in clinical practice to enhance sputum evacuation and lung recruitment. However, the evidence in different respiratory pathologies, especially in children, is still lacking. This systematic review aims to enlist the effectiveness of IPV as an airway clearance technique in pediatric patients. DATA SOURCES: A systematic literature search was performed in PubMed, Web of Science, and the Cochrane Library databases. STUDY SELECTION: Studies were included if the subjects suffered from a respiratory disease requiring airway clearance and the mean age of the sample was <18 years. After screening, nine articles remained for further analysis. RESULTS: Three of the nine articles examined patients with cystic fibrosis (CF). No significant differences in lung function or expectorated mucus were found compared to conventional chest physiotherapy. On the other hand, significant beneficial results were found for the treatment or prevention of atelectasis in non-CF patients using IPV. Similar results were seen when comparing therapies for neuromuscular/neurological patients. One study found that IPV reduced hospital stay and improved the clinical status of children with acute bronchiolitis compared to no physiotherapy. Severe adverse events did not occur in the included studies. CONCLUSION: A limited number of studies investigated IPV in the pediatric population. Despite the heterogeneity across the studies and the small sample sizes, the results seem promising. IPV is suggested to be a safe and effective alternative for airway clearance. Future research is required to confirm these results and to further analyze the possible benefits in different respiratory pathologies.