Challenges, Characteristics, and Outcomes of Chronic Pulmonary Aspergillosis: A 11-Year Experience in A Middle-Income Country.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a research priority in fungal diseases with a need for new studies to reduce misdiagnosis with more common diseases, discuss improvement in diagnostic methods and better characterize gaps in antifungal and surgical treatments to improve clinical outcomes. METHODS: In this retrospective study, we reviewed medical records of patients diagnosed with CPA from January 2010 to June 2021 at University of São Paulo, São Paulo, Brazil. We evaluated clinical characteristics, radiological findings, serology, treatment, and outcomes. RESULTS: The study included 91 participants, with 43 (47.3%) patients who underwent surgery and 69 (75.8%) received antifungal therapy. We found a predominance of middle-aged adults (median 51 years), males (n = 58, 64%) with lower BMI (median 21.3 kg/m2). The most common underlying lung disease was pulmonary tuberculosis (n = 70, 76.9%). The commonest symptoms were cough (n = 67, 74%), haemoptysis, and dyspnea (n = 63, 70%). The most common chest computerized tomography abnormalities were cavity (n = 86, 94.5%), with a predominance of mycetomas (n = 78, 91%). The serology was positive in 81% (61/75). The one-year mortality was low (3.3%). Clinical improvement and stability occurred in 89% of participants for constitucional symptoms and 86% for pulmonary symptoms. While serological improvement and stability occurred in 71%. Radiological improvement and stability occurred in 75%. CONCLUSION: We observed a good outcome after 1-year follow-up, in which the majority had improvement or stability of pulmonary and constitutional symptoms, decrease in CIE titers and low mortality.

Lung ultrasound versus chest computed tomography for pregnant inpatients with COVID-19.

PURPOSE: To compare lung ultrasound (US) and computed tomography (CT) in the assessment of pregnant women with COVID-19. METHODS: Prospective study comprising 39 pregnant inpatients with COVID-19 who underwent pulmonary assessment with CT and US with a maximum span of 48 h between the exams. The thorax was divided into 12 regions and assessed in terms of the following: the presence of B-lines (>2), coalescent B-lines, consolidation on US; presence of interlobular thickening, ground glass, consolidation on CT. The two methods were scored by adding up the scores from each thoracic region. RESULTS: A significant correlation was found between the scores obtained by the two methods (rICC = 0.946; p < 0.001). They were moderately in agreement concerning the frequency of altered pulmonary regions (weighted kappa = 0.551). In US, a score over 15, coalescent B-lines, and consolidation were predictors of the need for oxygen, whereas the predictors in CT were a lung score over 16 and consolidation. The two methods, US (p < 0.001; AUC = 0.915) and CT (p < 0.001; AUC = 0.938), were fairly accurate in predicting the need for oxygen. CONCLUSION: In pregnant women, lung US and chest CT are of similar accuracy in assessing lungs affected by COVID-19 and can predict the need for oxygen.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Organ doses evaluation for chest computed tomography procedures with TL dosimeters: Comparison with Monte Carlo simulations.

PURPOSE: To evaluate organ doses in routine and low-dose chest computed tomography (CT) protocols using an experimental methodology. To compare experimental results with results obtained by the National Cancer Institute dosimetry system for CT (NCICT) organ dose calculator. To address the differences on organ dose measurements using tube current modulation (TCM) and fixed tube current protocols. METHODS: An experimental approach to evaluate organ doses in pediatric and adult anthropomorphic phantoms using thermoluminescent dosimeters (TLDs) was employed in this study. Several analyses were performed in order to establish the best way to achieve the main results in this investigation. The protocols used in this study were selected after an analysis of patient data collected from the Institute of Radiology of the School of Medicine of the University of São Paulo (InRad). The image quality was evaluated by a radiologist from this institution. Six chest adult protocols and four chest pediatric protocols were evaluated. Lung doses were evaluated for the adult phantom and lung and thyroid doses were evaluated for the pediatric phantom. The irradiations were performed using both a GE and a Philips CT scanner. Finally, organ doses measured with dosimeters were compared with Monte Carlo simulations performed with NCICT. RESULTS: After analyzing the data collected from all CT examinations performed during a period of 3 yr, the authors identified that adult and pediatric chest CT are among the most applied protocol in patients in that clinical institution, demonstrating the relevance on evaluating organ doses due to these examinations. With regards to the scan parameters adopted, the authors identified that using 80 kV instead of 120 kV for a pediatric chest routine CT, with TCM in both situations, can lead up to a 28.7% decrease on the absorbed dose. Moreover, in comparison to the standard adult protocol, which is performed with fixed mAs, TCM, and ultra low-dose protocols resulted in dose reductions of up to 35.0% and 90.0%, respectively. Finally, the percent differences found between experimental and Monte Carlo simulated organ doses were within a 20% interval. CONCLUSIONS: The results obtained in this study measured the impact on the absorbed dose in routine chest CT by changing several scan parameters while the image quality could be potentially preserved.

"Interstitial lung abnormalities": translation to and use in Portuguese.

Objective: To conduct a survey on the use of the term "interstitial lung abnormalities" in radiology reports in Brazil, propose an appropriate Portuguese-language translation for the term, and provide a brief review of the literature on the topic. Materials and Methods: A survey was sent via electronic message to various radiologists in Brazil, asking about their familiarity with the term, which translation of the term they use in Portuguese, and whether they use the criteria proposed by the Fleischner Society. Results: A total of 163 responses were received, from all regions of Brazil. Although the vast majority (88%) of the respondents stated that they were familiar with the term "interstitial lung abnormalities", there was considerable variation regarding the equivalent term they used in Portuguese. Conclusion: We suggest that the term "anormalidades pulmonares intersticiais" be used in order to standardize radiology reports and disseminate knowledge of these findings in Brazil.

Objetivo: Fazer um levantamento sobre o uso do termo interstitial lung abnormalities nos laudos radiológicos no Brasil, propor uma tradução para o termo e fazer uma breve revisão sobre o tema. Materiais e Métodos: Foi enviada uma pesquisa, por meio de mensagem eletrônica, para diversos radiologistas de todo o Brasil, questionando sobre a familiarização com o termo, qual tradução em português utilizam e se usam os critérios propostos pela diretriz da Sociedade Fleischner. Resultados: Foram recebidas 163 respostas de todas as regiões do Brasil e a grande maioria dos radiologistas respondeu estar familiarizado com o termo interstitial lung abnormalities (88%), mas houve grande variação em relação ao termo utilizado como tradução para o português. Conclusão: Sugerimos a padronização do termo "anormalidades pulmonares intersticiais", a fim de uniformizar os relatórios radiológicos e difundir esta entidade no País.

Post-COVID-19 respiratory sequelae two years after hospitalization: an ambidirectional study.

Background: COVID-19 lung sequelae can impact the course of patient lives. We investigated the evolution of pulmonary abnormalities in post-COVID-19 patients 18-24 months after hospital discharge. Methods: A cohort of COVID-19 patients admitted to the Hospital das Clínicas da Faculdade de Medicina da USP in São Paulo, Brazil, between March and August of 2020, were followed-up 6-12 months after hospital discharge. A subset of patients with pulmonary involvement and chest computed tomography (CT) scans were eligible to participate in this second follow-up (18-24 months). Data was analyzed in an ambidirectional manner, including retrospective data from the hospitalization, and from the first follow-up (6-12 months after discharge), and compared with the prospective data collected in this new follow-up. Findings: From 348 patients eligible, 237 (68%) participated in this follow-up. Among participants, 139 (58%) patients presented ground-glass opacities and reticulations, and 80 (33%) presented fibrotic-like lesions (traction bronchiectasis and architectural distortion). Five (2%) patients improved compared to the 6-12-month assessment, but 20 (25%) of 80 presented worsening of lung abnormalities. For those with relevant assessments on both occasions, comparing the CT findings between this follow-up with the previous assessment, there was an increase in patients with architectural distortion (43 [21%] of 204 vs 57 [28%] of 204, p = 0.0093), as well as in traction bronchiectasis (55 [27%] of 204 vs 69 [34%] of 204, p = 0.0043). Patients presented a persistent functional impairment with demonstrated restrictive pattern in both follow-ups (87 [42%] of 207 vs 91 [44%] of 207, p = 0.76), as well as for the reduced diffusion capacity (88 [42%] of 208 vs 87 [42%] of 208, p = 1.0). Length of hospitalization (OR 1.04 [1.01-1.07], p = 0.0040), invasive mechanical ventilation (OR 3.11 [1.3-7.5] p = 0.011), patient's age (OR 1.03 [1.01-1.06] p = 0.0074 were consistent predictors for development of fibrotic-like lung lesions in post-COVID-19 patients. Interpretation: Post-COVID-19 lung sequelae can persist and progress after hospital discharge, suggesting airways involvement and formation of new fibrotic-like lesions, mainly in patients who were in intensive care unit (ICU). Funding: São Paulo Research Foundation (22/01769-5) and Instituto Todos pela Saúde (C1721).

Postmortem chest computed tomography in COVID-19: A minimally invasive autopsy method.

Objectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology. Methods: Twenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis. Results: There was a positive correlation between patient mean CT and histopathological severity score indexes - Pearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground-glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between ground-glass opacities extension and exudative diffuse alveolar damage in histological slides (R=-0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =-0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p ≥ 0.10). Conclusions: A minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground-glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported. Methods: In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment. Results: SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1ß serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Tomographic pleuropulmonary manifestations in rheumatoid arthritis: a pictorial essay.

Rheumatoid arthritis (RA) is an autoimmune inflammatory and heterogeneous disease that affects several systems, especially the joints. Among the extra-articular manifestations of RA, pleuropulmonary involvement occurs frequently, with different presentations, potentially in all anatomic thoracic compartments, and may determine high morbidity and mortality. The most common pleuropulmonary manifestations in patients with RA include interstitial lung disease (ILD), pleural disease, pulmonary arterial hypertension, rheumatoid lung nodules, airway disease (bronchiectasis and bronchiolitis), and lymphadenopathy. Pulmonary hypertension and ILD are the manifestations with the greatest negative impact in prognosis. HRCT of the chest is essential in the evaluation of patients with RA with respiratory symptoms, especially those with higher risk factors for ILD, such as male gender, smoking, older age, high levels of rheumatoid factor, or positive anti-cyclic citrullinated peptide antibody results. Additionally, other etiologies that may determine tomographic pleuropulmonary manifestations in patients with RA are infections, neoplasms, and drug-induced lung disease. In these scenarios, clinical presentation is heterogeneous, varying from being asymptomatic to having progressive respiratory failure. Knowledge on the potential etiologies causing tomographic pleuropulmonary manifestations in patients with RA coupled with proper clinical reasoning is crucial to diagnose and treat these patients.

Sensitivity of Antigen, Serology, and Microbiology Assays for Diagnosis of the Subtypes of Chronic Pulmonary Aspergillosis at a Teaching Hospital in São Paulo, Brazil.

Chronic pulmonary aspergillosis (CPA) is divided into five subtypes. The diagnosis of CPA is complicated due to poor sensitivity of the laboratory tests. Diagnostic performance of different antigen, serological, and microbiological methods in subtypes of CPA is unknown. The purpose of this study was to evaluate the diagnostic performance in different subtypes of CPA. A total of 91 participants with CPA were included, and the study was performed at Hospital das Clínicas of University of São Paulo. Bronchoalveolar lavage galactomannan (73%, 11/15), serology by immunodiffusion test (81%, 61/75), and histology (78%, 39/50) had the best sensitivity. The counterimmunoelectrophoresis (CIE) titers had a significant statistical difference between the CPA subtypes (P < 0.001), in which the forms chronic fibrosing pulmonary aspergillosis (CFPA) and subacute invasive aspergillosis (SAIA) had higher titers: 1/64 (interquartile range [IQR]: 1/32-1/256) and 1/64 (1/32-1/128). C-reactive protein generally presented lower values (median 15 mg/L, IQR: 6-33), with higher values in SAIA and lower values for Aspergillus nodule. Overall, we found a low diagnostic sensitivity of current tests. Regarding the CPA subtypes, we did not find great differences in the performance of the tests, but it is observed that the inflammatory markers and CIE titers tend to be higher in forms of the more extensive lung parenchyma involvement, such as SAIA and CFPA.

Diagnostic reference level quantities for adult chest and abdomen-pelvis CT examinations: correlation with organ doses.

OBJECTIVES: To evaluate correlations between DRL quantities (DRLq) stratified into patient size groups for non-contrast chest and abdomen-pelvis CT examinations in adult patients and the corresponding organ doses. METHODS: This study presents correlations between DRLq  (CTDIvol, DLP and SSDE) stratified into patient size ranges and corresponding organ doses shared in four groups: inside, peripheral, distributed and outside. The demographic, technical and dosimetric parameters were used to identify the influence of these quantities in organ doses. A robust statistical method was implemented in order to establish these correlations and its statistical significance. RESULTS: Median values of the grouped organ doses are presented according to the effective diameter ranges. Organ doses in the regions inside the imaged area are higher than the organ doses in peripheral, distributed and outside regions, excepted to the peripheral doses associated with chest examinations. Different levels of statistical significance between organ doses and the DRLq were presented. CONCLUSIONS: Correlations between DRLq and target-organ doses associated with clinical practice can support guidance's to the establishment of optimization criteria. SSDE demonstrated to be significant in the evaluation of organ doses is also highlighted. The proposed model allows the design of optimization actions with specific risk-reduction results.

Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: Prospective cohort study.

BACKGROUND: Coronavirus disease (COVID-19) survivors exhibit multisystemic alterations after hospitalization. Little is known about long-term imaging and pulmonary function of hospitalized patients intensive care unit (ICU) who survive COVID-19. We aimed to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and identify risk factors associated with chest computed tomography (CT) lesion severity. METHODS: A prospective cohort study of COVID-19 patients admitted to a tertiary hospital ICU in Brazil (March-August/2020), and followed-up six-twelve months after hospital admission. Initial assessment included: modified Medical Research Council dyspnea scale, SpO2 evaluation, forced vital capacity, and chest X-Ray. Patients with alterations in at least one of these examinations were eligible for CT and pulmonary function tests (PFTs) approximately 16 months after hospital admission. Primary outcome: CT lesion severity (fibrotic-like or non-fibrotic-like). Baseline clinical variables were used to build a machine learning model (ML) to predict the severity of CT lesion. RESULTS: In total, 326 patients (72%) were eligible for CT and PFTs. COVID-19 CT lesions were identified in 81.8% of patients, and half of them showed mild restrictive lung impairment and impaired lung diffusion capacity. Patients with COVID-19 CT findings were stratified into two categories of lesion severity: non-fibrotic-like (50.8%-ground-glass opacities/reticulations) and fibrotic-like (49.2%-traction bronchiectasis/architectural distortion). No association between CT feature severity and altered lung diffusion or functional restrictive/obstructive patterns was found. The ML detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity(sensitivity,0.78±0.02;specificity,0.79±0.01;F1-score,0.78±0.02;positive predictive rate,0.78±0.02; accuracy,0.78±0.02; and area under the curve,0.83±0.01). CONCLUSION: ICU hospitalization due to COVID-19 led to respiratory system alterations six-twelve months after hospital admission. Male sex and critical disease acute phase, characterized by a longer ICU and IMV period, and need for tracheostomy and vasoactive drugs, were risk factors for severe CT lesions six-twelve months after hospital admission.

Chronic lung lesions in COVID-19 survivors: predictive clinical model.

OBJECTIVE: This study aimed to propose a simple, accessible and low-cost predictive clinical model to detect lung lesions due to COVID-19 infection. DESIGN: This prospective cohort study included COVID-19 survivors hospitalised between 30 March 2020 and 31 August 2020 followed-up 6 months after hospital discharge. The pulmonary function was assessed using the modified Medical Research Council (mMRC) dyspnoea scale, oximetry (SpO2), spirometry (forced vital capacity (FVC)) and chest X-ray (CXR) during an in-person consultation. Patients with abnormalities in at least one of these parameters underwent chest CT. mMRC scale, SpO2, FVC and CXR findings were used to build a machine learning model for lung lesion detection on CT. SETTING: A tertiary hospital in Sao Paulo, Brazil. PARTICIPANTS: 749 eligible RT-PCR-confirmed SARS-CoV-2-infected patients aged ≥18 years. PRIMARY OUTCOME MEASURE: A predictive clinical model for lung lesion detection on chest CT. RESULTS: There were 470 patients (63%) that had at least one sign of pulmonary involvement and were eligible for CT. Almost half of them (48%) had significant pulmonary abnormalities, including ground-glass opacities, parenchymal bands, reticulation, traction bronchiectasis and architectural distortion. The machine learning model, including the results of 257 patients with complete data on mMRC, SpO2, FVC, CXR and CT, accurately detected pulmonary lesions by the joint data of CXR, mMRC scale, SpO2 and FVC (sensitivity, 0.85±0.08; specificity, 0.70±0.06; F1-score, 0.79±0.06 and area under the curve, 0.80±0.07). CONCLUSION: A predictive clinical model based on CXR, mMRC, oximetry and spirometry data can accurately screen patients with lung lesions after SARS-CoV-2 infection. Given that these examinations are highly accessible and low cost, this protocol can be automated and implemented in different countries for early detection of COVID-19 sequelae.

Quantitative CT Analysis in Chronic Hypersensitivity Pneumonitis: A Convolutional Neural Network Approach.

RATIONALE AND OBJECTIVES: Chronic hypersensitivity pneumonitis (cHP) is a heterogeneous condition, where both small airway involvement and fibrosis may simultaneously occur. Computer-aided analysis of CT lung imaging is increasingly used to improve tissue characterization in interstitial lung diseases (ILD), quantifying disease extension, and progression. We aimed to quantify via a convolutional neural network (CNN) method the extent of different pathological classes in cHP, and to determine their correlation to pulmonary function tests (PFTs) and mosaic attenuation pattern. MATERIALS AND METHODS: The extension of six textural features, including consolidation (C), ground glass opacity (GGO), fibrosis (F), low attenuation areas (LAA), reticulation (R) and healthy regions (H), was quantified in 27 cHP patients (age: 56 ± 11.5 years, forced vital capacity [FVC]% = 57 ± 17) acquired at full-inspiration via HRCT. Each class extent was correlated to PFTs and to mosaic attenuation pattern. RESULTS: H showed a positive correlation with FVC%, FEV1% (forced expiratory volume), total lung capacity%, and diffusion of carbon monoxide (DLCO)% (r = 0.74, r = 0.78, r = 0.73, and r = 0.60, respectively, p < 0.001). GGO, R and C negatively correlated with FVC% and FEV1% with the highest correlations found for R (r = -0.44, and r = -0.46 respectively, p < 0.05); F negatively correlated with DLCO% (r = -0.42, p < 0.05). Patients with mosaic attenuation pattern had significantly more H (p = 0.04) and lower R (p = 0.02) and C (p = 0.0009) areas, and more preserved lung function indices (higher FVC%; p = 0.04 and DLCO%; p = 0.05), but did not show more air trapping in lung function tests. CONCLUSION: CNN quantification of pathological tissue extent in cHP improves its characterization and shows correlation with PFTs. LAA can be overestimated by visual, qualitative CT assessment and mosaic attenuation pattern areas in cHP represents patchy ILD rather than small-airways disease.

A Convolutional Neural Network Approach to Quantify Lung Disease Progression in Patients with Fibrotic Hypersensitivity Pneumonitis (HP).

Rationale and Objectives To evaluate associations between longitudinal changes of quantitative CT parameters and spirometry in patients with fibrotic hypersensitivity pneumonitis (HP). Materials and Methods Serial CT images and spirometric data were retrospectively collected in a group of 25 fibrotic HP patients. Quantitative CT analysis included histogram parameters (median, interquartile range, skewness, and kurtosis) and a pretrained convolutional neural network (CNN)-based textural analysis, aimed at quantifying the extent of consolidation (C), fibrosis (F), ground-glass opacity (GGO), low attenuation areas (LAA) and healthy tissue (H). Results At baseline, FVC was 61(44-70) %pred. The median follow-up period was 1.4(0.8-3.2) years, with 3(2-4) visits per patient. Over the study, 8 patients (32%) showed a FVC decline of more than 5%, a significant worsening of all histogram parameters (p≤0.015) and an increased extent of fibrosis via CNN (p=0.038). On histogram analysis, decreased skewness and kurtosis were the parameters most strongly associated with worsened FVC (respectively, r2=0.63 and r2=0.54, p<0.001). On CNN classification, increased extent of fibrosis and consolidation were the measures most strongly correlated with FVC decline (r2=0.54 and r2=0.44, p<0.001). Conclusion CT histogram and CNN measurements provide sensitive measures of functional changes in fibrotic HP patients over time. Increased fibrosis was associated with FVC decline, providing index of disease progression. CNN may help improve fibrotic HP follow-up, providing a sensitive tool for progressive interstitial changes, which can potentially contribute to clinical decisions for individualizing disease management.

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series.

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).