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.

Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). METHODS: Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-ß expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. RESULTS: The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. CONCLUSION: LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).

Implementation and Results of a Dedicated Telemedicine Program (TeleTrachea) for Patients with Tracheal Diseases.

Background: Central airway diseases requiring frequent outpatient visits to a specialized medical center due to tracheal devices. Many of these patients have mobility and cognition restrictions or require specialized transport due to the need for supplemental oxygen. This study describes the implementation and results of a telemedicine program dedicated to patients with central airway diseases based in a Brazilian public health system. Methods: A retrospective study of telemedicine consultation for patients with central airway diseases referred to a public academic hospital between August 1, 2020 and August 1, 2022. The consultations occurred in a telemedicine department using the hospital's proprietary platform. Data retrieved consisted of demographics, disease characteristics, and the treatment modalities of the patients. The analysis included the savings in kilometers not traveled, the carbon footprint based on reducing CO2 emissions, and the cost savings in transportation. Results: A total of 1,153 telemedicine visits conducted in 516 patients (median age of 31.5 years). Two hundred ninety patients (56.2%) had a tracheal device (129 silicone T-Tube, 128 tracheostomy, and 33 endoprosthesis) and 159 patients (30.8%) had difficulties in transportation to the specialized medical center. Patients were served from 147 Brazilian cities from 22 states. The savings in kilometers traveled was 1,224,108.54 km, corresponding to a 250.14 ton reduction in CO2 emissions. The costs savings in transportation for the municipalities was BRL$ 1,272,283.78. Conclusions: Telemedicine consultations for patients with central airway diseases are feasible and safe. Cost savings and the possibility of disseminating specialized care make telemedicine a fundamental tool in current medical practice.

Risk Factors for the Impairment of Ambulation in Older People Hospitalized with COVID-19: A Retrospective Cohort Study.

(1) Background: Some older people hospitalized with COVID-19 have experienced reduced ambulation capacity. However, the prevalence of the impairment of ambulation capacity still needs to be established. Objective: To estimate the prevalence of, and identify the risk factors associated with, the impairment of ambulation capacity at the point of hospital discharge for older people with COVID-19. (2) Methods: A retrospective cohort study. Included are those with an age > 60 years, of either sex, hospitalized due to COVID-19. Clinical data was collected from patients' medical records. Ambulation capacity prior to COVID-19 infection was assessed through the patients' reports from their relatives. Multiple logistic regressions were performed to identify the risk factors associated with the impairment of ambulation at hospital discharge. (3) Results: Data for 429 older people hospitalized with COVID-19 were randomly collected from the medical records. Among the 56.4% who were discharged, 57.9% had reduced ambulation capacity. Factors associated with reduced ambulation capacity at discharge were a hospital stay longer than 20 days (Odds Ratio (OR): 3.5) and dependent ambulation capacity prior to COVID-19 (Odds Ratio (OR): 11.3). (4) Conclusion: More than half of the older people who survived following hospitalization due to COVID-19 had reduced ambulation capacity at hospital discharge. Impaired ambulation prior to the infection and a longer hospital stay were risks factors for reduced ambulation capacity.

Telemedicine in Brazil: Teleconsultations at the Largest University Hospital in the Country.

The coronavirus disease (COVID-19) pandemic leveraged telemedicine worldwide mainly due to the need for social distancing, patient safety, and infection prevention. The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) was a key reference site in the treatment of COVID-19 severe cases in the country. To continue patient's health care, it became necessary to increase the number of teleconsultations and standardize it institutionally. Herein, we briefly described how the HCFMUSP improved the teleconsultation health care service during the COVID-19 pandemic, highlighting the implementation of important innovations and the throughout standardization process, including patients and professional workflow. We also detailed the methodology used to implement or improve teleconsultation in a medical/multidisciplinary specialty at HCFMUSP. All these efforts made the HCFMUSP reach the goal of converting 15% of all face-to-face consultations into teleconsultations only in 2021. In addition, there were more than 370,000 teleconsultations until the end of 2022. Our experience has shown that having a supporting team, a digital certification process, and the data integration were key factors toward the successful implementation of the teleconsultation services. We believe that progressing toward teleconsultation will improve the population covered by health care services in Brazil, as well as contribute to a reduction of waiting time, and solving costs to health care institutions and patients. We expect this report of our experience in teleconsultation implementation could inspire and guide other health care institutions in the development of telemedicine.

Tele-Intensive Care Unit Program in Brazil: Implementation and Expansion.

In this scientific report, we aimed to describe the implementation and expansion of a Tele-Intensive Care Unit (Tele-ICU) program in Brazil, highlighting the pillars of success, improvements, and perspectives. Tele-ICU program emerged during the COVID-19 pandemic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), focusing on clinical case discussions and training of health practitioners in public hospitals of the state of São Paulo in Brazil, to support health care professionals for treating COVID-19 patients. The success of implementing this initiative endorsed the project expansion to other five hospitals from different macroregions of the country, leading to the Tele-ICU-Brazil. These projects assisted 40 hospitals, allowing more than 11,500 teleinterconsultations (exchange of medical information between health care professionals using a licensed online platform) and training more than 14,800 health care professionals, reducing mortality and length of hospitalized patients. A segment in telehealth for the obstetrics health care was implemented after detecting these were a susceptible group of patients to COVID-19 severity. As a perspective, this segment will be expanded to 27 hospitals in the country. The Tele-ICU projects reported here were the largest digital health ICU programs ever established in Brazilian National Health System until know. Their results were unprecedented and proved to be crucial for supporting health care professionals nationwide during the COVID-19 pandemic and guide future initiatives in digital health in Brazil's National Health System.

Functional impact on adults and older people after hospitalization by Covid-19.

BACKGROUND AND OBJECTIVES: Hospitalization by Covid-19 can cause persistent functional consequences after hospital discharge due to direct and indirect effects of SARS-COV-2 in several organs and systems of the body added to post-intensive care syndrome and prolonged bed rest. These impacts can lead to dependency in activities of daily living, mainly in older people due to aging process and functional decline. This study aimed to compare the effects of hospitalization by Covid-19 on functional capacity of adults and older people and to identify its associated factors. METHODS: Cross-sectional observational study of 159 survivors of hospitalization by Covid-19 after 1 month from discharge at Hospital das Clínicas of the University of São Paulo, divided into groups: adults (aged < 60 years) and older people (aged ≥ 60 years). Those who did not accept to participate, without availability or without ability to understand the questionnaires were excluded. Functional capacity was assessed by the Barthel Index and patients were classified according to their scores. Data analysis was performed in JASP Statistics program and the sample was compared between the age groups. Wilcoxon test was applied to compare before and after periods, Mann-Whitney test was used for between groups comparison. We adopted alpha = 0.05. RESULTS: The total Barthel Index median score was lower 1 month after hospital discharge than in the pre-Covid-19 period. Older people had worse functional status than adults before and also showed greater impairment after hospital discharge. Both groups showed lower Barthel Index classification than before, and older people presented more functional dependence than adults in both periods. Age, sarcopenia and frailty were associated factors. DISCUSSION: Hospitalization by Covid-19 impacts functional capacity after 1 month from discharge, especially in older people. Age, sarcopenia and frailty are associated factors. These results suggest need for care and rehabilitation of Covid-19 survivors.

Validation of an overnight wireless high-resolution oximeter for the diagnosis of obstructive sleep apnea at home.

Obstructive sleep apnea (OSA) is extremely common and has several consequences. However, most cases remain undiagnosed. One limitation is the lack of simple and validated methods for OSA diagnosis at home. The aim of this study was to validate a wireless high-resolution oximeter with a built-in accelerometer linked to a smartphone with automated cloud analysis (Biologix) that was compared with a home sleep test (HST, Apnea Link Air) performed on the same night. We recruited 670 patients out of a task force of 1013 patients with suspected OSA who were referred to our center for diagnosis. The final sample consisted of 478 patients (mean age: 56.7 ± 13.1 years, mean body mass index: 31.9 ± 6.3 kg/m2). To estimate the night-to-night OSA severity variability, 62 patients underwent HST for two consecutive nights. The HST-apnea-hypopnea index (AHI) and the Biologix-oxygen desaturation index (ODI) was 25.0 ± 25.0 events/h and 24.9 ± 26.5 events/h, respectively. The area under the curve-sensibility/specificity to detect at least mild (HST-AHI > 5), moderate-to-severe (HST-AHI > 15), and severe OSA (HST-AHI > 30) were (0.983)-94.7/92.8, (0.986)-94.8/93.9, and (0.990)-95.8/94.3, respectively. The limits of agreement originating from the Bland-Altman plot and the correlation between HST-AHI and Biologix-ODI were lower than the night-to-night HST-AHI variability (25.5 and 34.5 events/h, respectively, p = 0.001). We conclude that Biologix is a simple and reliable technique for OSA diagnosis at home.

Mortality over time among COVID-19 patients hospitalized during the first surge of the pandemic: A large cohort study.

BACKGROUND: Capacity strain negatively impacts patient outcome, and the effects of patient surge are a continuous threat during the COVID-19 pandemic. Evaluating changes in mortality over time enables evidence-based resource planning, thus improving patient outcome. Our aim was to describe baseline risk factors associated with mortality among COVID-19 hospitalized patients and to compare mortality rates over time. METHODS: We conducted a retrospective cohort study in the largest referral hospital for COVID-19 patients in Sao Paulo, Brazil. We investigated risk factors associated with mortality during hospitalization. Independent variables included age group, sex, the Charlson Comorbidity Index, admission period according to the stage of the first wave of the epidemic (early, peak, and late), and intubation. RESULTS: We included 2949 consecutive COVID-19 patients. 1895 of them were admitted to the ICU, and 1473 required mechanical ventilation. Median length of stay in the ICU was 10 (IQR 5-17) days. Overall mortality rate was 35%, and the adjusted odds ratios for mortality increased with age, male sex, higher Charlson Comorbidity index, need for mechanical ventilation, and being admitted to the hospital during the wave peak of the epidemic. Being admitted to the hospital during the wave peak was associated with a 33% higher risk of mortality. CONCLUSIONS: In-hospital mortality was independently affected by the epidemic period. The recognition of modifiable operational variables associated with patient outcome highlights the importance of a preparedness plan and institutional protocols that include evidence-based practices and allocation of resources.

Brazilian guidelines for the treatment of outpatients with suspected or confirmed COVID-19. A joint guideline of the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Medical Association (AMB), Brazilian Society of Angiology and Vascular Surgery (SBACV), Brazilian Society of Geriatrics and Gerontology (SBGG), Brazilian Society of Infectious Diseases (SBI), Brazilian Society of Family and Community Medicine (SBFMC), and Brazilian Thoracic Society (SBPT).

BACKGROUND: Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. METHODS: A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. RESULTS: Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. CONCLUSION: To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.

Distinct Outcomes in COVID-19 Patients with Positive or Negative RT-PCR Test.

Identification of the SARS-CoV-2 virus by RT-PCR from a nasopharyngeal swab sample is a common test for diagnosing COVID-19. However, some patients present clinical, laboratorial, and radiological evidence of COVID-19 infection with negative RT-PCR result(s). Thus, we assessed whether positive results were associated with intubation and mortality. This study was conducted in a Brazilian tertiary hospital from March to August of 2020. All patients had clinical, laboratory, and radiological diagnosis of COVID-19. They were divided into two groups: positive (+) RT-PCR group, with 2292 participants, and negative (-) RT-PCR group, with 706 participants. Patients with negative RT-PCR testing and an alternative most probable diagnosis were excluded from the study. The RT-PCR(+) group presented increased risk of intensive care unit (ICU) admission, mechanical ventilation, length of hospital stay, and 28-day mortality, when compared to the RT-PCR(-) group. A positive SARS-CoV-2 RT-PCR result was independently associated with intubation and 28 day in-hospital mortality. Accordingly, we concluded that patients with a COVID-19 diagnosis based on clinical data, despite a negative RT-PCR test from nasopharyngeal samples, presented more favorable outcomes than patients with positive RT-PCR test(s).

Timing to Intubation COVID-19 Patients: Can We Put It Off until Tomorrow?

BACKGROUND: The decision to intubate COVID-19 patients receiving non-invasive respiratory support is challenging, requiring a fine balance between early intubation and risks of invasive mechanical ventilation versus the adverse effects of delaying intubation. This present study analyzes the association between intubation day and mortality in COVID-19 patients. METHODS: We performed a unicentric retrospective cohort study considering all COVID-19 patients consecutively admitted between March 2020 and August 2020 requiring invasive mechanical ventilation. The primary outcome was all-cause mortality within 28 days after intubation, and a Cox model was used to evaluate the effect of time from onset of symptoms to intubation in mortality. RESULTS: A total of 592 (20%) patients of 3020 admitted with COVID-19 were intubated during study period, and 310 patients who were intubated deceased 28 days after intubation. Each additional day between the onset of symptoms and intubation was significantly associated with higher in-hospital death (adjusted hazard ratio, 1.018; 95% CI, 1.005-1.03). CONCLUSION: Among patients infected with SARS-CoV-2 who were intubated and mechanically ventilated, delaying intubation in the course of symptoms may be associated with higher mortality. TRIAL REGISTRATION: The study protocol was approved by the local Ethics Committee (opinion number 3.990.817; CAAE: 30417520.0.0000.0068).

Brazilian guidelines for the treatment of outpatients with suspected or confirmed COVID-19. A joint guideline of the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Medical Association (AMB), Brazilian Society of Angiology and Vascular Surgery (SBACV), Brazilian Society of Geriatrics and Gerontology (SBGG), Brazilian Society of Infectious Diseases (SBI), Brazilian Society of Family and Community Medicine (SBFMC), and Brazilian Thoracic Society (SBPT)

ABSTRACT Background Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. Methods A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. Results Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. Conclusion To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.

COVID-19 convalescent plasma cohort study: Evaluation of the association between both donor and recipient neutralizing antibody titers and patient outcomes.

BACKGROUND: Current evidence regarding COVID-19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID-19. METHODS: Prospective cohort including 102 patients with COVID-19 transfused with ABO compatible CCP on days 0-2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)-free days and the number of invasive mechanical ventilation-free days. RESULTS: Both nAbs of CCP units transfused (p < 0.001) and nAbs of patients before CCP transfusions (p = 0.028) were associated with clinical improvements by day 14. No significant associations between nAbs of patients or CCP units transfused were observed in the number of ICU or mechanical ventilation-free days. Administration of CCP units after 10 days of symptom onset resulted in a decrease in ICU-free days (p < 0.001) and mechanical ventilation-free days (p < 0.001). CONCLUSION: Transfusion of high titer nAbs CCP units may be a determinant in clinical strategies against COVID-19. We consider these data as useful parameters to guide future CCP transfusion practices.

Thoracoabdominal asynchrony associates with exercise intolerance in fibrotic interstitial lung diseases.

BACKGROUND AND OBJECTIVE: The precise coordination of respiratory muscles during exercise minimizes work of breathing and avoids exercise intolerance. Fibrotic interstitial lung disease (f-ILD) patients are exercise-intolerant. We assessed whether respiratory muscle incoordination and thoracoabdominal asynchrony (TAA) occur in f-ILD during exercise, and their relationship with pulmonary function and exercise performance. METHODS: We compared breathing pattern, respiratory mechanics, TAA and respiratory muscle recruitment in 31 f-ILD patients and 31 healthy subjects at rest and during incremental cycle exercise. TAA was defined as phase angle (PhAng) >20°. RESULTS: During exercise, when compared with controls, f-ILD patients presented increased and early recruitment of inspiratory rib cage muscle (p < 0.05), and an increase in PhAng, indicating TAA. TAA was more frequent in f-ILD patients than in controls, both at 50% of the maximum workload (42.3% vs. 10.7%, p = 0.01) and at the peak (53.8% vs. 23%, p = 0.02). Compared with f-ILD patients without TAA, f-ILD patients with TAA had lower lung volumes (forced vital capacity, p < 0.01), greater dyspnoea (Medical Research Council > 2 in 64.3%, p = 0.02), worse exercise performance (lower maximal work rate % predicted, p = 0.03; lower tidal volume, p = 0.03; greater desaturation and dyspnoea, p < 0.01) and presented higher oesophageal inspiratory pressures with lower gastric inspiratory pressures and higher recruitment of scalene (p < 0.05). CONCLUSION: Exercise induces TAA and higher recruitment of inspiratory accessory muscle in ILD patients. TAA during exercise occurred in more severely restricted ILD patients and was associated with exertional dyspnoea, desaturation and limited exercise performance.

Tracking the time course of pathological patterns of lung injury in severe COVID-19.

BACKGROUND: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. METHODS: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. RESULTS: Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. CONCLUSION: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.

Diaphragmatic ultrasound findings correlate with dyspnea, exercise tolerance, health-related quality of life and lung function in patients with fibrotic interstitial lung disease.

BACKGROUND: Fibrotic interstitial lung disease (FILD) patients are typically dyspneic and exercise-intolerant with consequent impairment of health-related quality of life (HRQoL). Respiratory muscle dysfunction is among the underlying mechanisms of dyspnea and exercise intolerance in FILD but may be difficult to diagnose. Using ultrasound, we compared diaphragmatic mobility and thickening in FILD cases and healthy controls and correlated these findings with dyspnea, exercise tolerance, HRQoL and lung function. METHODS: We measured diaphragmatic mobility and thickness during quiet (QB) and deep breathing (DB) and calculated thickening fraction (TF) in 30 FILD cases and 30 healthy controls. We correlated FILD cases' diaphragmatic findings with dyspnea, exercise tolerance (six-minute walk test), lung function and HRQoL (St. George's Respiratory Questionnaire). RESULTS: Diaphragmatic mobility was similar between groups during QB but was lower in FILD cases during DB when compared to healthy controls (3.99 cm vs 7.02 cm; p <  0.01). FILD cases showed higher diaphragm thickness during QB but TF was lower in FILD when compared to healthy controls (70% vs 188%, p <  0.01). During DB, diaphragmatic mobility and thickness correlated with lung function, exercise tolerance and HRQoL, but inversely correlated with dyspnea. Most FILD cases (70%) presented reduced TF, and these patients had higher dyspnea and exercise desaturation, lower HRQoL and lung function. CONCLUSION: Compared to healthy controls, FILD cases present with lower diaphragmatic mobility and thickening during DB that correlate to increased dyspnea, decreased exercise tolerance, worse HRQoL and worse lung function. FILD cases with reduced diaphragmatic thickening are more dyspneic and exercise-intolerant, have lower HRQoL and lung function.

Forced Oscillation Technique and Small Airway Involvement in Chronic Hypersensitivity Pneumonitis.

OBJECTIVE: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of specific organic antigens or low-molecular weight substances in genetically susceptible individuals. Although small airway involvement is prominent in patients with chronic HP, conventional pulmonary function tests (PFTs) are relatively insensitive to identify it. Thus, the authors aimed to evaluate resistance (R5) and reactance (X5) values at 5Hz on inspiration, expiration, and whole breath, as well as small airway resistance (R5-19) values using a forced oscillation technique (FOT) in patients with chronic HP, and their responses after bronchodilator. In addition, R5 and X5 values according to the presence or absence of mosaic attenuation on computed tomography (CT) were compared. METHODS: PFTs with plethysmography, diffusing capacity of the lungs for carbon monoxide (DLCO) and FOT measurements were performed pre-bronchodilator and post-bronchodilator. High-resolution CT was performed at the same visit, and classified according to the presence or absence of mosaic attenuation. R5 and X5 values were then compared according to the presence or absence of mosaic attenuation on CT. RESULTS: Twenty-eight patients with chronic HP (57.1% female; mean age, 56±11.5 years; mean forced vital capacity 57±17% predicted) were evaluated. All patients had low X5 values, reflecting lower lung compliance, and only three (8%) demonstrated elevated R5 (whole-breath) values. No patients exhibited bronchodilator response in R5, X5 and R5-19 values. In patients who exhibited greater extension of mosaic attenuation (n=11), R5 and X5 values could not discriminate those with a greater presence of these areas on CT. CONCLUSIONS: The results suggest that FOT does not help to additionally characterise concomitant small airway involvement in patients with chronic fibrotic HP who demonstrate restrictive ventilatory pattern in conventional PFTs. Nevertheless, FOT appeared to better characterise decreased lung compliance due to fibrosis through X5. Bronchodilator therapy did not appear to induce an acute response in chronic HP patients with restrictive disease. The precise role of FOT in subacute HP and obstructive chronic HP, therefore, must be evaluated.

Unilateral diaphragm paralysis: a dysfunction restricted not just to one hemidiaphragm.

BACKGROUND: Most patients with unilateral diaphragm paralysis (UDP) have unexplained dyspnea, exercise limitations, and reduction in inspiratory muscle capacity. We aimed to evaluate the generation of pressure in each hemidiaphragm separately and its contribution to overall inspiratory strength. METHODS: Twenty-seven patients, 9 in right paralysis group (RP) and 18 in left paralysis group (LP), with forced vital capacity (FVC) < 80% pred, and 20 healthy controls (CG), with forced expiratory volume in 1 s (FEV1) > 80% pred and FVC > 80% pred, were evaluated for lung function, maximal inspiratory (MIP) and expiratory (MEP) pressure measurements, diaphragm ultrasound, and transdiaphragmatic pressure during magnetic phrenic nerve stimulation (PdiTw). RESULTS: RP and LP had significant inspiratory muscle weakness compared to controls, detected by MIP (- 57.4 ± 16.9 for RP; - 67.1 ± 28.5 for LP and - 103.1 ± 30.4 cmH2O for CG) and also by PdiTW (5.7 ± 4 for RP; 4.8 ± 2.3 for LP and 15.3 ± 5.7 cmH2O for CG). The PdiTw was reduced even when the non-paralyzed hemidiaphragm was stimulated, mainly due to the low contribution of gastric pressure (around 30%), regardless of whether the paralysis was in the right or left hemidiaphragm. On the other hand, in CG, esophagic and gastric pressures had similar contribution to the overall Pdi (around 50%). Comparing both paralyzed and non-paralyzed hemidiaphragms, the mobility during quiet and deep breathing, and thickness at functional residual capacity (FRC) and total lung capacity (TLC), were significantly reduced in paralyzed hemidiaphragm. In addition, thickness fraction was extremely diminished when contrasted with the non-paralyzed hemidiaphragm. CONCLUSIONS: In symptomatic patients with UDP, global inspiratory strength is reduced not only due to weakness in the paralyzed hemidiaphragm but also to impairment in the pressure generated by the non-paralyzed hemidiaphragm.