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 craniocervical flexion and neck endurance exercises plus pulmonary rehabilitation on pulmonary function in spinal cord injury: a pilot single-blinded randomised controlled trial.

STUDY DESIGN: Randomised controlled trial with computerised allocation, assessor blinding and intention-to-treat analysis. OBJECTIVE: This study wanted to prove that cervicocranial flexion exercise (CCFE) and superficial neck flexor endurance training combined with common pulmonary rehabilitation is feasible for improving spinal cord injury people's pulmonary function. SETTING: Taoyuan General Hospital, Ministry of Health and Welfare: Department of Physiotherapy, Taiwan. METHOD: Thirteen individuals who had sustained spinal cord injury for less than a year were recruited and randomised assigned into two groups. The experimental group was assigned CCFEs and neck flexor endurance training plus normal cardiopulmonary rehabilitation. The control group was assigned general neck stretching exercises plus cardiopulmonary rehabilitation. Lung function parameters such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow rate (PEFR), inspiratory capacity (IC), dyspnoea, pain, and neck stiffness were recorded once a week as short-term outcome measure. RESULT: The experimental group showed significant time effects for FVC (pre-therapy: 80.4 ± 21.4, post-therapy: 86.9 ± 16.9, p = 0.021, 95% CI: 0.00-0.26) and PEFR (pre-therapy: 67.0 ± 33.4; post-therapy: 78.4 ± 26.9, p = 0.042, 95% CI: 0.00-0.22) after the therapy course. Furthermore, the experimental group showed significant time effects for BDI (experimental group: 6.3 ± 3.0; control group: 10.8 ± 1.6, p = 0.012, 95% CI: 0.00-0.21). CONCLUSION: The exercise regime for the experimental group could efficiently increase lung function due to the following three reasons: first, respiratory accessory muscle endurance increases through training. Second, posture becomes less kyphosis resulting increasing lung volume. Third, the ratio between superficial and deep neck flexor is more synchronised. IRB TRIAL REGISTRATION: TYGH108045. CLINICAL TRIAL REGISTRATION: NCT04500223.

Effects of a pulmonary rehabilitation program on pulmonary function, exercise performance, and quality of life in patients with severe COVID-19.

BACKGROUND: Severe coronavirus 2019 disease (COVID-19) causes acute hypoxemic respiratory failure requiring invasive mechanical ventilation (IMV). Once these symptoms are resolved, patients can present systemic deterioration. OBJECTIVE: The two objectives of this study were as follows: to describe the results of a pulmonary rehabilitation program (PRP), which is divided into three groups with different numbers of sessions (12, 24, and 36), and to associate the variables of pulmonary function, exercise performance, and functionality with the number of sessions and functional improvement. DESIGN: Prospective, observational study. METHODS: PRP consisted of aerobic + strength + flexibility exercises under the supervision and individualized into 12, 24, or 36 sessions (12s, 24s, and 36s), depending on the evolution of each patient. At the beginning of the study and immediately after the intervention, forced vital capacity (FVC), maximal inspiratory pressure, 6-minute walk test (6MWT), sit-to-stand test (STS), maximal handgrip strength (HGS), Fatigue Assessment Scale, Post-COVID-19 Functional Status (PCFS), and health-related quality of life (HRQoL) were measured. RESULTS: The proposed PRP demonstrated a positive effect on pulmonary function, exercise performance, and HRQoL, regardless of the number of sessions. A higher score on the PCFS and more days on IMV were associated with the increased likelihood of needing more sessions, whereas more meters on the 6MWT in the initial evaluation was associated with a reduced likelihood of needing more sessions. Finally, more repetitions on the STS and less distance covered on the initial 6MWT were associated with a greater improvement in exercise performance evaluated with the 6MWT. CONCLUSION: Supervised and individualized PRP for patients with severe post-COVID-19 improves pulmonary function, exercise performance, functionality, and quality of life. Functionality, distance covered on the 6MWT, and the days on IMV are central to the scheduling of the number of sessions for these patients.

Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab. METHODS: We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety. RESULTS: 48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51-0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27-0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09-0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI -0.46--0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26-0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile. CONCLUSIONS: This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.

Gait differences between COPD and healthy controls: systematic review and meta-analysis.

BACKGROUND: Despite the importance of gait as a determinant of falls, disability and mortality in older people, understanding of gait impairment in COPD is limited. This study aimed to identify differences in gait characteristics during supervised walking tests between people with COPD and healthy controls. METHODS: We searched 11 electronic databases, supplemented by Google Scholar searches and manual collation of references, in November 2019 and updated the search in July 2021. Record screening and information extraction were performed independently by one reviewer and checked for accuracy by a second. Meta-analyses were performed in studies not considered at a high risk of bias. RESULTS: Searches yielded 21 085 unique records, of which 25 were included in the systematic review (including 1015 people with COPD and 2229 healthy controls). Gait speed was assessed in 17 studies (usual speed: 12; fast speed: three; both speeds: two), step length in nine, step duration in seven, cadence in six, and step width in five. Five studies were considered at a high risk of bias. Low-quality evidence indicated that people with COPD walk more slowly than healthy controls at their usual speed (mean difference (MD) -19 cm·s-1, 95% CI -28 to -11 cm·s-1) and at a fast speed (MD -30 cm·s-1, 95% CI -47 to -13 cm·s-1). Alterations in other gait characteristics were not statistically significant. CONCLUSION: Low-quality evidence shows that people with COPD walk more slowly than healthy controls, which could contribute to an increased falls risk. The evidence for alterations in spatial and temporal components of gait was inconclusive. Gait impairment appears to be an important but understudied area in COPD.

Correlation between early postnatal body weight changes and lung ultrasound scores as predictors of bronchopulmonary dysplasia in preterm infants: A secondary analysis of a prospective study.

Recent research links early weight changes (EWC) with bronchopulmonary dysplasia (BPD) in preterm neonates, while lung ultrasound score (LUS) has shown promise in predicting BPD. We aimed to explore the correlation between LUS and EWC as markers of extravascular lung edema and to investigate the correlation between LUS and EWC in preterm infants with respiratory distress syndrome regarding future BPD development. This secondary analysis of a prospective study involved infants ≤ 28 weeks gestation. Enrolled infants underwent lung ultrasound assessment on postnatal days 3, 7 and 14, measuring LUS. EWC was computed on the same time points. Infants were classified as either having BPD or not. Descriptive statistics, correlation coefficient, and area under the receiver operating characteristic (AUROC) curve analysis were utilized. Of 132 infants, 70 (53%) had BPD. Univariate analysis revealed statistically significant differences in LUS and EWC at days 3, 7, and 14 between BPD and no-BPD groups (p < 0.001). A statistically significant but weak positive correlation existed between LUS and EWC (r0.37, r0.29, r0.24, and p < 0.01) at postnatal days 3, 7, and 14, respectively. AUROC analysis indicated LUS having superior predictive capacity for the need for invasive mechanical ventilation at day 14 as well as the later BPD development compared to EWC (p < 0.0001). CONCLUSION: In a cohort of extreme preterm infants, our study revealed a positive yet weak correlation between LUS and EWC, suggesting that EWC was not the major contributing to the evolving chronic lung disease. WHAT IS KNOWN: • Recent evidence links Early Weight-Changes with bronchopulmonary dysplasia in preterm neonates. • Lung ultrasound score has shown promise in early prediction of the subsequent development of bronchopulmonary dysplasia in preterm infants. No studies have examined the correlation between Early Weight-Changes and Lung ultrasound score in preterm infants during first 2 weeks after birth. WHAT IS NEW: • Our study demonstrated a positive and statistically significant correlation between early LUS and EWC, indicating their potential role as early predictors for the subsequent development of BPD in extreme preterm infants. • The weak correlation between the two parameters may stem from the possible restricted influence of EWC, given that it may not be the primary factor contributing to the evolving chronic lung disease.

Genetic and observational associations of lung function with gastrointestinal tract diseases: pleiotropic and mendelian randomization analysis.

BACKGROUND: The two-way communications along the gut-lung axis influence the immune function in both gut and lung. However, the shared genetic characteristics of lung function with gastrointestinal tract (GIT) diseases remain to be investigated. METHODS: We first investigated the genetic correlations between three lung function traits and four GIT diseases. Second, we illustrated the genetic overlap by genome-wide pleiotropic analysis (PLACO) and further pinpointed the relevant tissue and cell types by partitioning heritability. Furthermore, we proposed pleiotropic genes as potential drug targets by drug database mining. Finally, we evaluated the causal relationships by epidemiologic observational study and Mendelian randomization (MR) analysis. RESULTS: We found lung function and GIT diseases were genetically correlated. We identified 258 pleiotropic loci, which were enriched in gut- and lung-specific regions marked by H3K4me1. Among these, 16 pleiotropic genes were targets of drugs, such as tofacitinib and baricitinib targeting TYK2 for the treatment of ulcer colitis and COVID-19, respectively. We identified a missense variant in TYK2, exhibiting a shared causal effect on FEV1/FVC and inflammatory bowel disease (rs12720356, PPLACO=1.38 × 10- 8). These findings suggested TYK2 as a promising drug target. Although the epidemiologic observational study suggested the protective role of lung function in the development of GIT diseases, no causalities were found by MR analysis. CONCLUSIONS: Our study suggested the shared genetic characteristics between lung function and GIT diseases. The pleiotropic variants could exert their effects by modulating gene expression marked by histone modifications. Finally, we highlighted the potential of pleiotropic analyses in drug repurposing.

Clinical Implications of Removing Race-Corrected Pulmonary Function Tests for African American Patients Requiring Surgery for Lung Cancer.

Importance: Removal of race correction in pulmonary function tests (PFTs) is a priority, given that race correction inappropriately conflates race, a social construct, with biological differences and falsely assumes worse lung function in African American than White individuals. However, the impact of decorrecting PFTs for African American patients with lung cancer is unknown. Objectives: To identify how many hospitals providing lung cancer surgery use race correction, examine the association of race correction with predicted lung function, and test the effect of decorrection on surgeons' treatment recommendations. Design, Setting, and Participants: In this quality improvement study, hospitals participating in a statewide quality collaborative were contacted to determine use of race correction in PFTs. For hospitals performing race correction, percent predicted preoperative and postoperative forced expiratory volume in 1 second (FEV1) was calculated for African American patients who underwent lung cancer resection between January 1, 2015, and September 31, 2022, using race-corrected and race-neutral equations. US cardiothoracic surgeons were then randomized to receive 1 clinical vignette that differed by the use of Global Lung Function Initiative equations for (1) African American patients (percent predicted postoperative FEV1, 49%), (2) other race or multiracial patients (percent predicted postoperative FEV1, 45%), and (3) race-neutral patients (percent predicted postoperative FEV1, 42%). Main Outcomes and Measures: Number of hospitals using race correction in PFTs, change in preoperative and postoperative FEV1 estimates based on race-neutral or race-corrected equations, and surgeon treatment recommendations for clinical vignettes. Results: A total of 515 African American patients (308 [59.8%] female; mean [SD] age, 66.2 [9.4] years) were included in the study. Fifteen of the 16 hospitals (93.8%) performing lung cancer resection for African American patients during the study period reported using race correction, which corresponds to 473 African American patients (91.8%) having race-corrected PFTs. Among these patients, the percent predicted preoperative FEV1 and postoperative FEV1 would have decreased by 9.2% (95% CI, -9.0% to -9.5%; P < .001) and 7.6% (95% CI, -7.3% to -7.9%; P < .001), respectively, if race-neutral equations had been used. A total of 225 surgeons (194 male [87.8%]; mean [SD] time in practice, 19.4 [11.3] years) were successfully randomized and completed the vignette items regarding risk perception and treatment outcomes (76% completion rate). Surgeons randomized to the vignette with African American race-corrected PFTs were more likely to recommend lobectomy (79.2%; 95% CI, 69.8%-88.5%) compared with surgeons randomized to the other race or multiracial-corrected (61.7%; 95% CI, 51.1%-72.3%; P = .02) or race-neutral PFTs (52.8%; 95% CI, 41.2%-64.3%; P = .001). Conclusions and Relevance: Given the findings of this quality improvement study, surgeons should be aware of changes in PFT testing because removal of race correction PFTs may change surgeons' treatment decisions and potentially worsen existing disparities in receipt of lung cancer surgery among African American patients.

Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema. Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.