Radio-Histological Correlation of Lung Features in Severe COVID-19 Through CT-Scan and Lung Ultrasound Evaluation.

Background: Patients with coronavirus disease 2019 (COVID-19) can develop severe bilateral pneumonia leading to respiratory failure. Lung histological samples were scarce due to the high risk of contamination during autopsies. We aimed to correlate histological COVID-19 features with radiological findings through lung ultrasound (LU)-guided postmortem core needle biopsies (CNBs) and computerized tomography (CT) scans. Methodology: We performed an observational prospective study, including 30 consecutive patients with severe COVID-19. The thorax was divided into 12 explorations regions to correlate LU and CT-scan features. Histological findings were also related to radiological features through CNBs. Results: Mean age was 62.56 ± 13.27 years old, with 96.7% male patients. Postmortem LU-guided CNBs were performed in 13 patients. Thirty patients were evaluated with both thoracic LU and chest CT scan, representing a total of 279 thoracic regions explored. The most frequent LU finding was B2-lines (49.1%). The most CT-scan finding was ground-glass opacity (GGO, 29%). Pathological CT-scan findings were commonly observed when B2-lines or C-lines were identified through LU (positive predictive value, PPV, 87.1%). Twenty-five postmortem echo-guided histological samples were obtained from 12 patients. Histological samples showed diffuse alveolar damage (DAD) (75%) and chronic interstitial inflammation (25%). The observed DAD was heterogeneous, showing multiple evolving patterns of damage, including exudative (33.3%), fibrotic (33.3%), and organizing (8.3%) phases. In those patients with acute or exudative pattern, two lesions were distinguished: classic hyaline membrane; fibrin "plug" in alveolar space (acute fibrinous organizing pneumonia, AFOP). C-profile was described in 33.3% and presented histological signs of DAD and lung fibrosis. The predominant findings were collagen deposition (50%) and AFOP (50%). B2-lines were identified in 66.7%; the presence of hyaline membrane was the predominant finding (37.5%), then organizing pneumonia (12.5%) and fibrosis (37.5%). No A-lines or B1-lines were observed in these patients. Conclusion: LU B2-lines and C-profile are predominantly identified in patients with severe COVID-19 with respiratory worsening, which correspond to different CT patterns and histological findings of DAD and lung fibrosis.

Lung Transplant Improves Survival and Quality of Life Regardless of Telomere Dysfunction.

Introduction: Fibrotic interstitial lung diseases (ILDs) are the first indication for lung transplantation (LT). Telomere dysfunction has been associated with poor post-transplant outcomes. The aim of the study was to evaluate the morbi-mortality and quality of life in fibrotic ILDs after lung transplant depending on telomere biology. Methods: Fibrotic ILD patients that underwent lung transplant were allocated to two arms; with or without telomere dysfunction at diagnosis based on the telomere length and telomerase related gene mutations revealed by whole-exome sequencing. Post-transplant evaluation included: (1) short and long-term mortality and complications and (2) quality of life. Results: Fifty-five percent of patients that underwent LT carried rare coding mutations in telomerase-related genes. Patients with telomere shortening more frequently needed extracorporeal circulation and presented a higher rate of early post-transplant hematological complications, longer stay in the intensive care unit (ICU), and a higher number of long-term hospital admissions. However, post-transplant 1-year survival was higher than 80% regardless of telomere dysfunction, with improvement in the quality of life and oxygen therapy withdrawal. Conclusions: Post-transplant morbidity is higher in patients with telomere dysfunction and differs according to elapsed time from transplantation. However, lung transplant improves survival and quality of life and the associated complications are manageable.

Lung Ultrasound Score to Predict Outcomes in COVID-19.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can develop severe bilateral pneumonia leading to respiratory failure. We aimed to study the potential role of lung ultrasound score (LUS) in subjects with COVID-19. METHODS: We conducted an observational, prospective pilot study, including consecutive subjects admitted to an intermediate care unit due to COVID-19 pneumonia. LUS is a 12-zone examination method for lung parenchyma assessment. LUS was performed with a portable convex transducer, scores from 0 to 36 points. Clinical and demographic data were collected at LUS evaluation. Survival analysis was performed using a composite outcome including ICU admission or death. Subjects were followed for 30 d from LUS assessment. RESULTS: Of 36 subjects included, 69.4% were male, and mean age was 60.19 ± 12.75 y. A cutoff LUS ≥ 24 points showed 100% sensitivity, 69.2% specificity, and an area under the receiver operating characteristic curve of 0.85 for predicting worse prognosis. The composite outcome was present in 10 subjects (55.6%) with LUS ≥ 24 points, but not in the group with lower LUS scores (P < .001). Subjects with LUS ≥ 24 points had a higher risk of ICU admission or death (hazard ratio 9.97 [95% CI 2.75-36.14], P < .001). Significant correlations were observed between LUS and [Formula: see text], serum D-dimer, C-reactive protein, lactate dehydrogenase, and lymphocyte count. CONCLUSIONS: LUS ≥ 24 points can help identify patients with COVID-19 who are likely to require ICU admission or to die during follow-up. LUS also correlates significantly with clinical and laboratory markers of COVID-19 severity.

Mapping IPF helps identify geographic regions at higher risk for disease development and potential triggers.

BACKGROUND AND OBJECTIVE: The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis (IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross-analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development. METHODS: This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data. RESULTS: In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent. CONCLUSION: In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.

Host- and Pathogen-Related Factors for Acute Cardiac Events in Pneumococcal Pneumonia.

BACKGROUND: Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce. METHODS: A retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs. RESULTS: Of 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11-3.13). CONCLUSIONS: ACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies.

Rituximab effect in severe progressive connective tissue disease-related lung disease: preliminary data.

Progressive connective tissue disease (CTD)-related lung disease is a challenging condition that requires lung transplantation in some patients. Treatment with rituximab may improve lung function. To evaluate the effect of rituximab in patients with progressive CTD-related lung disease who met criteria for inclusion in waiting list for a lung transplant. Retrospective study of patients with progressive CTD-related lung disease with criteria for lung transplant (FVC < 60% and/or DLCO < 40%) that started treatment with rituximab because of disease progression. Clinical variables, pulmonary function tests and chest computed tomography were used to monitor the effect of rituximab. The cohort included 18 patients; systemic sclerosis (7), rheumatoid arthritis (5), systemic lupus erythematosus (4), Sjögren syndrome (1) and antisynthetase syndrome (1). The radiologic patterns observed were: usual interstitial pneumonia (1), non-specific interstitial pneumonia (9), lymphoid interstitial pneumonia (1), emphysema-usual interstitial pneumonia (1), shrinking lung syndrome (3) and undetermined pattern (3). Over the previous year to rituximab initiation a decline in FVC (- 3.8%, p = 0.095) and DLCO (- 8.4%, p = 0.004) was observed. After 2 years of treatment, DLCO significantly improved (+ 12.4%, p < 0.001 at 1 year and + 15.3%, p = 0.001 at 2 years). Six patients (33.3%) presented adverse events related to rituximab. No patient required lung transplant or died during the study period. Rituximab is an effective treatment for patients with severe and progressive CTD-related lung disease, which allows to delay lung transplantation in some cases.

Effectiveness of an intensive weight-loss program for severe OSA in patients undergoing CPAP treatment: a randomized controlled trial.

STUDY OBJECTIVES: To determine whether an intensive weight-loss program (IWLP) is effective for reducing weight, the severity of obstructive sleep apnea (OSA), and metabolic variables in patients with obesity and severe OSA undergoing continuous positive airway pressure treatment. METHODS: Forty-two patients were randomized to the control (CG, n = 20) or the intervention group (IG, n = 22), who followed a 12-month IWLP. The primary outcome was a reduction in the apnea-hypopnea index (AHI) as measured at 3 and 12 months by full polysomnography. Metabolic variables, blood pressure, body fat composition by bioimpedance, carotid intima media thickness, and visceral fat by computed tomography were also assessed. RESULTS: Mean age was 49 (6.7) years, body mass index 35 (2.7) kg/m², and AHI 69 (20) events/h. Weight reduction was higher for the IG than the CG at 3 and 12 months, -10.5 versus -2.3 kg (P < .001), and -8.2 versus -0.1 kg (P < .001), respectively, as was loss of visceral fat at 12 months. AHI decreased more in the IG at 3 months (-23.72 versus -9 events/h) but the difference was not significant at 12 months, though 28% of patients from the IG had an AHI < 30 events/h compared to none in the CG (P = .046). At 12 months, the IG showed a reduction in C-reactive protein (P = .013), glycated hemoglobin (P = .031) and an increase in high density lipoprotein cholesterol (P = .027). CONCLUSIONS: An IWLP in patients with obesity and severe OSA is effective for reducing weight and OSA severity. It also results in an improvement in lipid profiles, glycemic control, and inflammatory markers. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Effectiveness of an Intensive Weight Loss Program for Obstructive Sleep Apnea Syndrome (OSAS) Treatment; Identifier: NCT02832414; URL: https://clinicaltrials.gov/ct2/show/record/NCT02832414.

Infectiousness of patients with smear-negative pulmonary tuberculosis, assessed by Real-time Polymerase Chain Reaction, XpertⓇMTB/RIF.

Currently, pulmonary tuberculosis (TB) isolation recommendations are based on serial sputum smear microscopy. To assess infectiousness of smear-negative/GeneXpert-positive (Sm-/GXpert+) pulmonary TB, we evaluated 511 contacts of pulmonary TB patients attended at a teaching hospital in Spain (2010-2018). There were no statistically significant differences in rates of Mycobacterium tuberculosis infection (46.2% contacts of smear-positive and 34.6% contacts of Sm-/GXpert+ pulmonary TB patients, p = 0.112). Sm-/GXpert+ pulmonary TB poses a substantial risk of transmission of M. tuberculosis infection. Our results add evidence to support including Real-time Polymerase Chain Reaction (XpertⓇMTB/RIF) in the work-up diagnosis of suspected pulmonary TB cases to make decisions on air-borne isolation.

Anthropometrical phenotypes are important when explaining obstructive sleep apnea in female bariatric cohorts.

Central obesity is the main risk factor for obstructive sleep apnea (OSA). Whether there exists a central-obesity anthropometric that better explains apnea-hypopnea index (AHI) variability in the general population and in sleep cohorts is unknown, and this is even less explored among increasing grades of obesity. The objective of the study is to investigate whether there is an anthropometric that better explains AHI variability in a sample of morbidly obese women awaiting bariatric surgery (BS). A prospective multicentre cross-sectional study was conducted in consecutive women before BS. Demographic and anthropometric characteristics included age, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR). OSA was diagnosed by polysomnography. The capacity of anthropometrics to explain AHI variance was investigated using regression linear models. A total of 115 women were evaluated: age, 44 ± 10 years; BMI, 46 ± 5 kg/m2 ; AHI, 35 ± 26 events/hr. AHI was associated with all anthropometrics except weight, height and HC. The best univariate predictor was WHR, which accounted for 15% of AHI variance. The simplest model (age + BMI) accounted for 9%, which increased to 20% when applying more complex measurements (age + BMI + NC + WC + HC). The explanatory capacity did not change significantly when applying a simpler model (age + WHR + NC, 19%). In this female morbidly obese cohort, anthropometrics explained one-fifth of AHI variability. WHR is the best univariate parameter and models including waist and neck data provide more information than BMI when explaining AHI variability. Thus, even in young women with extreme obesity, OSA seems to be linked to a specific central-obesity phenotype rather than to a whole-obesity pattern.

Imbalance in the Expression of Genes Associated with Purinergic Signalling in the Lung and Systemic Arteries of COPD Patients.

Growing evidence indicates that purinergic signalling is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the vascular remodelling that occurs in other disorders; however, its role in initial vascular changes of COPD is not entirely known. We hypothesised that expression of genes regulating extracellular ATP and adenosine levels would be altered in the lung and systemic arteries of COPD patients. Quantitative real-time PCR was performed to analyse the relative expression of 17 genes associated with purinergic signalling and inflammation in lungs and intercostal arteries of never smokers (NS) (n = 16), non-obstructed smokers (NOS) (n = 17) and COPD patients (n = 21). Gene expression of ATP-degrading enzymes was decreased in both tissues of NOS and COPD patients compared to NS. NT5E expression (gene transcribing for an AMP hydrolyzing ectonucleotidase) was increased in both tissues in NOS compared to the other groups. P1 and P2 receptors did not show changes in expression. Expression of genes associated with inflammation (interleukin-13) was upregulated only in lung tissues of COPD. These findings suggest that the expression of different extracellular ATP-degrading enzymes is altered in smokers (NOS and COPD patients), promoting inflammation. However, the high NT5E expression found only in NOS could compensate this inflammatory environment.

Ultrathin Bronchoscopy with and without Virtual Bronchoscopic Navigation: Influence of Segmentation on Diagnostic Yield.

BACKGROUND: Bronchoscopy is a safe technique for diagnosing peripheral pulmonary lesions (PPLs), and virtual bronchoscopic navigation (VBN) helps guide the bronchoscope to PPLs. OBJECTIVES: We aimed to compare the diagnostic yield of VBN-guided and unguided ultrathin bronchoscopy (UTB) and explore clinical and technical factors associated with better results. We developed a diagnostic algorithm for deciding whether to use VBN to reach PPLs or choose an alternative diagnostic approach. METHODS: We compared diagnostic yield between VBN-UTB (prospective cases) and unguided UTB (historical controls) and analyzed the VBN-UTB subgroup to identify clinical and technical variables that could predict the success of VBN-UTB. RESULTS: Fifty-five cases and 110 controls were included. The overall diagnostic yield did not differ between the VBN-guided and unguided arms (47 and 40%, respectively; p = 0.354). Although the yield was slightly higher for PPLs ≤20 mm in the VBN-UTB arm, the difference was not significant (p = 0.069). No other clinical characteristics were associated with a higher yield in a subgroup analysis, but an 85% diagnostic yield was observed when segmentation was optimal and the PPL was endobronchial (vs. 30% when segmentation was suboptimal and 20% when segmentation was optimal but the PPL was extrabronchial). CONCLUSIONS: VBN-guided UTB is not superior to unguided UTB. A greater impact of VBN-guided over unguided UTB is highly dependent on both segmentation quality and an endobronchial location of the PPL. Segmentation quality should be considered before starting a procedure, when an alternative technique that may improve yield can be chosen, saving time and resources.

Defining the role of neutrophil-to-lymphocyte ratio in COPD: a systematic literature review.

COPD is characterized by a pulmonary and systemic inflammatory process. Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations. The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count. We performed a systematic literature review using the PRISMA statement. Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls. Compared with controls, COPD patients had significantly higher NLR values. We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients. Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively). Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity. The NLR is an independent predictor of in-hospital and late mortality after exacerbation. In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR.

Positive Airway Pressure to Enhance Computed Tomography Imaging for Airway Segmentation for Virtual Bronchoscopic Navigation.

RATIONALE: Virtual bronchoscopic navigation (VBN) guidance to peripheral pulmonary lesions is often limited by insufficient segmentation of the peripheral airways. OBJECTIVES: To test the effect of applying positive airway pressure (PAP) during CT acquisition to improve segmentation, particularly at end-expiration. METHODS: CT acquisitions in inspiration and expiration with 4 PAP protocols were recorded prospectively and compared to baseline inspiratory acquisitions in 20 patients. The 4 protocols explored differences between devices (flow vs. turbine), exposures (within seconds vs. 15-min) and pressure levels (10 vs. 14 cmH2O). Segmentation quality was evaluated with the number of airways and number of endpoints reached. A generalized mixed-effects model explored the estimated effect of each protocol. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and lung function did not significantly differ between protocols. Compared to baseline inspiratory acquisitions, expiratory acquisitions after 15 min of 14 cmH2O PAP segmented 1.63-fold more airways (95% CI 1.07-2.48; p = 0.018) and reached 1.34-fold more endpoints (95% CI 1.08-1.66; p = 0.004). Inspiratory acquisitions performed immediately under 10 cmH2O PAP reached 1.20-fold (95% CI 1.09-1.33; p < 0.001) more endpoints; after 15 min the increase was 1.14-fold (95% CI 1.05-1.24; p < 0.001). CONCLUSIONS: CT acquisitions with PAP segment more airways and reach more endpoints than baseline inspiratory acquisitions. The improvement is particularly evident at end-expiration after 15 min of 14 cmH2O PAP. Further studies must confirm that the improvement increases diagnostic yield when using VBN to evaluate peripheral pulmonary lesions.

Addition of hyaluronic acid improves tolerance to 7% hypertonic saline solution in bronchiectasis patients.

BACKGROUND: The excessive retention of sputum in the airways, leading to pulmonary infections, is a common consequence of bronchiectasis. Although inhalation of 7% hypertonic saline (HS) has proven an effective method to help remove the mucus, many patients are intolerant of this treatment. The addition of 0.1% hyaluronic acid to HS (HS+HA) could increase tolerance to HS in these patients. The main objective of this study was to evaluate the tolerability of HS+HA in bronchiectasis patients who are intolerant to HS. METHODS: This prospective, observational, open-label study analysed the outcomes of two groups of bronchiectasis patients previously scheduled to start HS therapy. Patients were assessed for tolerance to HS by a questionnaire, spirometry and clinical evaluation. Patients who were intolerant were evaluated for tolerance to HS+HA approximately one week later. All patients were evaluated for their tolerance to HS or HS+HA 4 weeks after the start of their treatment. Patients were also assessed with quality-of-life and adherence questionnaires, and all adverse events were registered. RESULTS: A total of 137 bronchiectasis patients were enrolled in the study (age = 63.0 ± 14.7 years; 63.5% women). Of these, 92 patients (67.1%) were tolerant and 45 patients (32.9%) were intolerant to HS. Of the 45 patients intolerant to HS, 31 patients (68.9%) were tolerant and 14 patients (31.1%) intolerant to HS+HA. Of these 31 tolerant patients, 26 (83.9%) could complete the 4-week treatment with HS+HA. CONCLUSIONS: Two-thirds of bronchiectasis patients that presented intolerance to inhaled HS alone are tolerant to inhaled HS+HA, suggesting that HA improves tolerance to HS therapy.

Pulmonary Infections with Nontuberculous Mycobacteria, Catalonia, Spain, 1994-2014.

In Spain, systematic reporting of pulmonary infections with nontuberculous mycobacteria is not mandatory. Therefore, to determine trends, we retrospectively identified cases for January 1994-December 2014 in Catalonia. Over the 21 years, prevalence increased and was associated with being male. Mycobacterium avium complex and M. abscessus prevalence increased; M. kansasii prevalence decreased.

Is the purinergic pathway involved in the pathology of COPD? Decreased lung CD39 expression at initial stages of COPD.

BACKGROUND: Extracellular adenosine triphosphate (ATP) is up-regulated in the airways of patients with chronic obstructive pulmonary disease (COPD), resulting in increased inflammation, bronchoconstriction, and cough. Although extracellular ATP levels are tightly controlled by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1; also known as CD39) in the lungs, the role of CD39 in the pathology of COPD is unknown. We hypothesized that alterations in the expression and activity of CD39 could be part of the mechanisms for initiating and perpetuating the disease. METHODS: We analyzed CD39 gene and protein expression as well as ATPase enzyme activity in lung tissue samples of patients with COPD (n = 17), non-obstructed smokers (NOS) (n = 16), and never smokers (NS) (n = 13). Morphometry studies were performed to analyze pulmonary vascular remodeling. RESULTS: There was significantly decreased CD39 gene expression in the lungs of the COPD group (1.17 [0.85-1.81]) compared with the NOS group (1.88 [1.35-4.41]) and NS group (3.32 [1.23-5.39]) (p = 0.037). This attenuation correlated with higher systemic inflammation and intimal thickening of muscular pulmonary arteries in the COPD group. Lung CD39 protein levels were also lower in the COPD group (0.34 [0.22-0.92]) compared with the NOS group (0.67 [0.32-1.06]) and NS group (0.95 [0.4-1.1) (p = 0.133). Immunohistochemistry showed that CD39 was downregulated in lung parenchyma, epithelial bronchial cells, and the endothelial cells of pulmonary muscular arteries in the COPD group. ATPase activity in human pulmonary structures was reduced in the lungs of patients with COPD. CONCLUSION: An attenuation of CD39 expression and activity is presented in lung tissue of stable COPD patients, which could lead to pulmonary ATP accumulation, favoring the development of pulmonary inflammation and emphysema. This may be a mechanism underlying the development of COPD.