Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights.

BACKGROUND: Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. METHODS: We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. RESULTS: At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. CONCLUSIONS: Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

Proposal and Definition of an Intelligent Clinical Decision Support System Applied to the Prediction of Dyspnea after 12 Months of an Acute Episode of COVID-19.

Long COVID is a condition that affects a significant proportion of patients who have had COVID-19. It is characterised by the persistence of associated symptoms after the acute phase of the illness has subsided. Although several studies have investigated the risk factors associated with long COVID, identifying which patients will experience long-term symptoms remains a complex task. Among the various symptoms, dyspnea is one of the most prominent due to its close association with the respiratory nature of COVID-19 and its disabling consequences. This work proposes a new intelligent clinical decision support system to predict dyspnea 12 months after a severe episode of COVID-19 based on the SeguiCovid database from the Álvaro Cunqueiro Hospital in Vigo (Galicia, Spain). The database is initially processed using a CART-type decision tree to identify the variables with the highest predictive power. Based on these variables, a cascade of expert systems has been defined with Mamdani-type fuzzy-inference engines. The rules for each system were generated using the Wang-Mendel automatic rule generation algorithm. At the output of the cascade, a risk indicator is obtained, which allows for the categorisation of patients into two groups: those with dyspnea and those without dyspnea at 12 months. This simplifies follow-up and the performance of studies aimed at those patients at risk. The system has produced satisfactory results in initial tests, supported by an AUC of 0.75, demonstrating the potential and usefulness of this tool in clinical practice.

Evolution and long­term respiratory sequelae after severe COVID-19 pneumonia: nitric oxide diffusion measurement value.

INTRODUCTION: There are no published studies assessing the evolution of combined determination of the lung diffusing capacity for both nitric oxide and carbon monoxide (DLNO and DLCO) 12 months after the discharge of patients with COVID-19 pneumonia. METHODS: Prospective cohort study which included patients who were assessed both 3 and 12 months after an episode of SARS-CoV-2 pneumonia. Their clinical status, health condition, lung function testings (LFTs) results (spirometry, DLNO-DLCO analysis, and six-minute walk test), and chest X-ray/computed tomography scan images were compared. RESULTS: 194 patients, age 62 years (P25-75, 51.5-71), 59% men, completed the study. 17% required admission to the intensive care unit. An improvement in the patients' exercise tolerance, the extent of the areas of ground-glass opacity, and the LFTs between 3 and 12 months following their hospital discharge were found, but without a decrease in their degree of dyspnea or their self-perceived health condition. DLNO was the most significantly altered parameter at 12 months (19.3%). The improvement in DLNO-DLCO mainly occurred at the expense of the recovery of alveolar units and their vascular component, with the membrane factor only improving in patients with more severe infections. CONCLUSIONS: The combined measurement of DLNO-DLCO is the most sensitive LFT for the detection of the long-term sequelae of COVID-19 pneumonia and it explain better their pathophysiology.

[Effectiveness of nebulized hypertonic saline in patients with bronchial hypersecretion]. / Efectividad del suero salino hipertónico nebulizado en pacientes con hipersecreción bronquial.

INTRODUCTION: Nebulized hypertonic saline (HS) improves quality of life and reduces exacerbations in patients with cystic fibrosis. It is unknown if it would offer the same benefits in other hypersecretory pathologies. METHODS: Retrospective observational study. Patients who passed the tolerance test and started HS 5.8% with one year of follow-up were included. Clinical and healthcare parameters were quantified in the year before and after the start of treatment. RESULTS: 101 patients, 60.4% women, 65years (95%CI: 62.4-67.9): 82 (81.2%) bronchiectasis, 6 (5.9%) COPD, 2 (2%) asthma, 1 (1%) ILD, and 10 (9.9%) other causes. There was a reduction in bronchorrhea (91.1% vs 75.2%), recurrent infections (57.4% vs 22.8%) and cycles of antibiotic therapy (1.54 vs 0.55), as well as an increase in FEV1 (1881ml vs. 1942ml) and a decrease in visits to primary care (2.94 vs. 1.1), emergencies (0.36 vs. 0.17) and hospitalizations (0.17 vs. 0.17). 06). 73 patients (72.3%) presented an adequate tolerance. CONCLUSION: Nebulization of HS 5.8% in patients with bronchial hypersecretion is safe and has a remarkable clinical and healthcare impact.

The Diagnostic Contribution of Systematic Lung Ultrasonography in Patients Admitted to a Conventional Pulmonology Hospitalization Unit.

OBJECTIVE: Although the evidence to date remains limited, we hypothesized that performing protocolized lung ultrasound (LUS) in patients, admitted to a conventional pulmonology hospitalization unit, could improve diagnostic precision. The main objectives of this study were to evaluate the diagnostic contribution and changes in the treatments administered after performing a protocolized LUS in patients hospitalized in a Pulmonology Department ward. METHODOLOGY: This was a prospective, observational study, which included patients admitted from the Emergency Department to a conventional Pulmonology Department hospitalization unit, after first being evaluated by a pulmonologist. LUS was performed within the first 48 hours of admission. The diagnosis at the time of discharge was used as the reference diagnosis. RESULTS: A total of 180 patients were included in this study. The admitting diagnoses were the decompensation of an underlying obstructive disease in 60 patients (33.3%), respiratory infection in 93 (51.7%), pulmonary thromboembolism (PE) in 9 (5%), exacerbation of an interstitial lung disease in 14 (7.8%), and other causes in 4 cases (2.2%). Ultrasonography provided new information, unsuspected at the patient's admission, in 117 (65%) of the patients by capturing images suggestive of infection in 63 patients (35%), 1 new case of ILD, 23 (12.7%) cases of cardiogenic edema, and pleural pathology in 19 (10.5%), as well as two tumors and indirect data related to a PE. The use of LUS resulted in the decision to change the already established treatment in 17.2% of the cases. CONCLUSIONS: LUS provided additive information in more than half of patients that ended up reclassifying or potentially changing diagnosis or treatment. Thus, including LUS in management algorithms could reduce the need for other complementary tests or unnecessary treatments.

[Lung Ultrasound to Predict Unfavorable Progress in Patients Hospitalized for COVID-19]. / Predicción de evolución desfavorable en pacientes hospitalizados por COVID-19 mediante ecografía pulmonar.

OBJECTIVE: Thoracic ultrasound has been shown to be useful in the diagnosis of COVID-19 pulmonary involvement. Several scores for quantifying the degree of involvement have been described, although there is no evidence to show that they have any capacity for predicting unfavorable progress. METHODOLOGY: Prospective cohort study of patients hospitalized for COVID-19. The sample was stratified according to clinical course, and patients requiring invasive or non-invasive respiratory support were classified as having unfavorable progress. Biomarkers were analyzed at admission and on the same day that thoracic ultrasound was performed. Prognostic scales were also determined at admission. The ultrasound score was obtained in 8 or 14 areas, depending on the patient's ability to sit. RESULTS: We included 44 patients, 13 (29,5%) of whom subsequently needed ventilatory support. Eight areas were explored in all patients and 14 areas in 35 (79.5%). The most affected areas were the posterior lower lobes. Significant differences were found between the 2 groups on the SOFA and quick SOFA multidimensional scales, and PCR and LDH on the same day as thoracic ultrasound, and the ultrasound scores. The best area under the ROC curve (AUC) was obtained with the 14-area score, with a result of 0.88 (95% CI: 0.75-0.99). Its sensitivity and specificity for a cut-off score of 13.5 were 100% and 61.5%, respectively. CONCLUSIONS: The use of scores to quantify lung involvement measured by thoracic ultrasound provides useful information, facilitating risk stratification in patients hospitalized with COVID-19.

Validity of Lung Ultrasound: Is an Image Worth More Than a Thousand Sounds?

INTRODUCTION: There is debate as to whether lung-ultrasound (LUS) can replace lung-auscultation (LA) in the assessment of respiratory diseases. METHODOLOGY: The diagnostic validity, safety, and reliability of LA and LUS were analyzed in patients admitted in a pulmonary ward due to decompensated obstructive airway diseases, decompensated interstitial diseases, and pulmonary infections, in a prospective study. Standard formulas were used to calculate the diagnostic sensitivity, specificity, and accuracy. The interobserver agreement with respect to the LA and LUS findings was evaluated based on the Kappa coefficient (ᴋ). RESULTS: A total of 115 patients were studied. LUS was more sensitive than the LA in evaluating pulmonary infections (93.59% vs. 77.02%; p = 0.001) and more specifically in the case of decompensated obstructive airway diseases (95.6% vs. 19.10%; p = 0.001). The diagnostic accuracy of LUS was also greater in the case of pulmonary infections (75.65% vs. 60.90%; p = 0.02). The sensitivity and specificity of the combination of LA and LUS was 95.95%, 50% in pulmonary infections, 76.19%, 100% in case of decompensated obstructive airway diseases, and (100%, 88.54%) in case of interstitial diseases. (ᴋ) was 0.71 for an A-pattern, 0.73 for pathological B-lines, 0.94 for condensations, 0.89 for pleural-effusion, 0.63 for wheezes, 0.38 for rhonchi, 0.68 for fine crackles, 0.18 for coarse crackles, and 0.29 for a normal LA. CONCLUSIONS: There is a greater interobserver agreement in the interpretation of LUS-findings compared to that of LA-noises, their combined use improves diagnostic performance in all diseases examined.

Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion.

Three to four months after hospitalisation for COVID-19 pneumonia, the most frequently described alteration in respiratory function tests (RFTs) is decreased carbon monoxide transfer capacity (DLCO). METHODS: This is a prospective cohort study that included patients hospitalised because of SARS-CoV-2 pneumonia, three months after their discharge. A clinical evaluation, analytical parameters, chest X-ray, six-minute walk test, spirometry and DLCO-DLNO analysis were performed. Demographic variables, comorbidities, and variables related to the severity of the admission were recorded. RESULTS: Two hundred patients completed the study; 59.5% men, age 62 years, 15.5% admitted to the intensive care unit. The most frequent functional alteration, in 27% of patients, was in the DLCO-DLNO combination. This alteration was associated with age, male sex, degree of dyspnoea, poorer perception of health, and limited ability for physical effort. These patients also presented higher levels of D-Dimer and more residual radiological alterations. In 42% of the patients with diffusion alterations, only reduced DLNO was presented, along with lower D-Dimer levels and less capillary volume involvement. The severity of the process was associated with the reduction in DLCO-DLNO. CONCLUSIONS: The most sensitive RFT for the detection of the sequelae of COVID-19 pneumonia was the combined measurement of DLCO-DLNO and this factor was related to patient health status and their capacity for physical exertion. In 40% of these cases, there was only a reduction in DLNO, a finding that may indicate less pulmonary vascular involvement.

Validation of the portable Air-Smart Spirometer.

BACKGROUND: The Air-Smart Spirometer is the first portable device accepted by the European Community (EC) that performs spirometric measurements by a turbine mechanism and displays the results on a smartphone or a tablet. METHODS: In this multicenter, descriptive and cross-sectional prospective study carried out in 2 hospital centers, we compare FEV1, FVC, FEV1/FVC ratio measured with the Air Smart-Spirometer device and a conventional spirometer, and analyze the ability of this new portable device to detect obstructions. Patients were included for 2 consecutive months. We calculate sensitivity, specificity, positive and negative predictive value (PPV and NPV) and likelihood ratio (LR +, LR-) as well as the Kappa Index to evaluate the concordance between the two devices for the detection of obstruction. The agreement and relation between the values of FEV1 and FVC in absolute value and the FEV1/FVC ratio measured by both devices were analyzed by calculating the intraclass correlation coefficient (ICC) and the Pearson correlation coefficient (r) respectively. RESULTS: 200 patients (100 from each center) were included with a mean age of 57 (± 14) years, 110 were men (55%). Obstruction was detected by conventional spirometry in 73 patients (40.1%). Using a FEV1/FVC ratio smaller than 0.7 to detect obstruction with the Air Smart-Spirometer, the kappa index was 0.88, sensitivity (90.4%), specificity (97.2%), PPV (95.7%), NPV (93.7%), positive likelihood ratio (32.29), and negative likelihood ratio (0.10). The ICC and r between FEV1, FVC, and FEV1 / FVC ratio measured by the Air Smart Spirometer and the conventional spirometer were all higher than 0.94. CONCLUSION: The Air-Smart Spirometer is a simple and very precise instrument for detecting obstructive airway diseases. It is easy to use, which could make it especially useful non-specialized care and in other areas.

Clinical and molecular study of 4 cases of pulmonary hypertension associated with sarcoidosis.

Sarcoidosis is a pleomorphic disease that can present with pulmonary hypertension (PH). What little information is available about the association of these two diseases comes mainly from small series of patients scheduled for transplant. We present 4 cases of mild pulmonary involvement in whom right catheterisation was performed and PH-specific therapy was administered. After obtaining written consent, a genetic study was performed that showed mutations in PH-related genes in 3 of the patients. This is the first study of its kind to yield genetic information for this type of PH.

CCTTT pentanucleotide repeats in inducible nitric oxide synthase gene expression in patients with pulmonary arterial hypertension.

INTRODUCTION: One of the pathways involved in pulmonary arterial hypertension (PAH) is the nitric oxide (NO) pathway. A polymorphism in the inducible NO synthase (NOS2) gene has been described, consisting of the CCTTT pentanucleotide repeat, which causes a reduction in NO production. The aim of this study was to determine if this polymorphism increases susceptibility to developing PAH. METHODS: Sixty four patients with a diagnosis of PAH groupsi and iv and 50 healthy controls were compared. DNA genotyping of the samples for this polymorphism was performed using PCR. The distribution between both groups was compared and correlated with clinical and haemodynamic parameters and therapeutic response. RESULTS: A significantly different distribution was observed in the number of repeats between patients and controls (P<.0001). When the samples were categorised by short forms (both alleles with less than 12repeats) and long forms (≥12 repeats), it was observed that the former had an almost 4-fold risk of developing PAH (odds ratio: 3.83; 95%CI: 1.19-12.32, P=.024). There were no differences between the most common types of PAH, either in therapeutic response or survival. There was no correlation between haemodynamic parameters and the number of repeats in the patients, and only a weak correlation with systolic PAH. CONCLUSIONS: There are significant differences in the distribution of the NOS2 promotor CCTTT polymorphism between patients with PAH and the healthy population. A minor CCTTT pentanucleotide repeat in the NOS2 gene may increase the risk of developing PAH.