Clinical characteristics of complete responders versus non-complete responders to omalizumab, benralizumab and mepolizumab in patients with severe asthma: a long-term retrospective analysis.

BACKGROUND: Some patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients' characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice. METHODS: Data of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12 months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV1 >80% predicted. RESULTS: An improvement in all asthma control parameters was observed after 12 months of treatment and a mean follow-up of 55 months. After 12 months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern. CONCLUSIONS: This study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics.

Treatment with anti-IgE and anti-IL-5 biologics significantly improved clinical outcomes in severe asthma patients.The rate of complete responders of 27.2% at 12 months even increased to 35.3% at the end of a mean follow-up of 55 months.The persistence of an airflow obstructive pattern was the main cause of the failure to achieve complete response.

EBUS-TBNA for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer clinically staged with PET/CT.

BACKGROUND AND OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer (NSCLC) clinically staged with positron emission tomography/computed tomography (PET/CT). METHODS: We conducted a study that included patients with centrally located T1N0M0 NSCLC, clinically staged with PET/CT who underwent EBUS-TBNA for mediastinal staging. Patients with negative EBUS-TBNA underwent mediastinoscopy, video-assisted mediastinoscopic lymphadenectomy (VAMLA) and/or lung resection with systematic nodal dissection, that were considered the gold standard. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), overall accuracy of EBUS-TBNA for diagnosing mediastinal metastases (N2 disease) and the number needed to treat (NNT: number of patients needed to undergo EBUS-TBNA to avoid a case of pathologic N2 disease after resection) were calculated. RESULTS: One-hundred eighteen patients were included. EBUS-TBNA proved N2 disease in four patients. In the remaining 114 patients who underwent mediastinoscopy, VAMLA and/or resection there were two cases of N2 (N2 prevalence 5.1%). The sensitivity, specificity, NPV, PPV and overall accuracy for diagnosing mediastinal metastases (N2 disease) were of 66%, 100%, 98%, 100% and 98%, respectively. The NNT was 31 (95% CI: 15-119). CONCLUSION: EBUS-TBNA in patients with central clinically staged T1N0M0 NSCLC presents a good diagnostic accuracy for mediastinal staging, even in a population with low prevalence of N2 disease. Therefore, its indication should be considered in the management of even these early lung cancers.

Characterization and Factors Associated with Poor Asthma Control in Adults with Severe Eosinophilic Asthma.

A study was conducted in 98 adult patients diagnosed with severe eosinophilic asthma (73.5% women, mean age 47.2 years) and followed prospectively for 1 year. The aim of the study was to characterize this population and to identify factors associated with poor prognosis at 1 year of follow-up. At the initial visit, uncontrolled severe asthma was diagnosed in 87.7% of patients. Allergic sensitization was observed in 81.7% (polysensitization in 17.3%), with clinically significant allergic asthma in 45%. The mean percentage of sputum eosinophils was 4.7% (standard deviation(SD) 6.3%) and the mean (SD) blood eosinophil count 467 (225) cells/µL. Almost half of the patients (48.3%) had sputum eosinophilia (>3% eosinophils). Sputum eosinophils correlated significantly with peripheral eosinophilia (p = 0.004) and, to a lesser extent, with fractional exhaled nitric oxide (FeNO) (p = 0.04). After 1 year, 48 patients (49%) had uncontrolled asthma in all visits, and 50 (51%) had controlled asthma in some visits. Airway obstruction (FEV1 < 80% predicted) was the main reason for uncontrolled asthma. In the multivariate analysis, an obstructive pattern (odds ratio (OR) 7.45, 95% confidence interval (CI) 2.41-23.03, p < 0.0001) and the patient's age (OR 1.045, 95% CI 1.005-1.086, p = 0.026) were independent predictors of poor asthma control. In adult-onset and long-standing asthma, serum interleukin (IL) IL-17 was higher in the uncontrolled asthma group. This study contributes to characterizing patients with severe eosinophilic asthma in real-world clinical practice.

Impact of the COVID-19 pandemic on diagnosis of respiratory diseases in the Northern Metropolitan Area in Barcelona (Spain).

Objective: The COVID-19 pandemic has had a great effect on the management of chronic diseases, by limiting the access to primary care and to diagnostic procedures, causing a decline in the incidence of most diseases. Our aim was to analyze the impact of the pandemic on primary care new diagnoses of respiratory diseases. Methods: Observational retrospective study performed to describe the effect of COVID-19 pandemic on the incidence of respiratory diseases according to primary care codification. Incidence rate ratio between pre-pandemic and pandemic period was calculated. Results: We found a decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications (J95). Instead, we found increases in flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). Conclusion: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic.

Objetivo: La pandemia de COVID-19 ha tenido efecto sobre el seguimiento de las enfermedades crónicas. Nuestro objetivo fue analizar el impacto de la pandemia por COVID-19 en los nuevos diagnósticos respiratorios en atención primaria. Metodología: Estudio observacional retrospectivo realizado para describir el impacto de la COVID-19 sobre la incidencia de diagnósticos respiratorios en atención primaria. Se ha calculado la tasa relativa de incidencia entre el periodo prepandémico y el pandémico. Resultados: Hallamos una reducción en la incidencia de patología respiratoria (IRR 0,65) durante la pandemia. Al comparar los distintos grupos de enfermedades (CIE-10), encontramos una reducción significativa en el número de nuevos casos durante la pandemia, excepto en el caso de tuberculosis pulmonar, abscesos o necrosis pulmonar y otras complicaciones respiratorias. Por otro lado, se detectaron incrementos en nuevos diagnósticos de gripe y neumonía (IRR 2,17) y enfermedades respiratorias intersticiales (IRR 1,41). Conclusión: Se ha producido un descenso en el número de nuevos diagnósticos de la mayoría de las enfermedades respiratorias durante la pandemia por COVID-19.

Usefulness of Routine Bronchial Aspirate of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used for the study of intrathoracic lymphadenopathy and centrally tumours but no report has discussed the contribution of routine cytological and microbiological BA during the procedure. The aim of the study was to analyse the diagnostic yield of BA during EBUS, and to determine the potential cost reduction. METHODS: A prospective study of cytological and microbiological BA collected during EBUS-TBNA was conducted between January 2021 and June 2022. Demographic data, indication, previous BA bronchoscopy or EBUS diagnosis were recorded. The main variable tested was the number of patients in which the result of the BA obtained through EBUS-TBNA determined a change in the diagnosis. RESULTS: A total of 450 (70.9% male) patients were included. BA cytology showed abnormal cells in 33 (7.3%) of patients, and only 1 case (0.2%) provided a previously unknown diagnosis. All these cases were patients with suspected malignancy. BA microbiological samples found germens in 30 (6.7%) patients but only in 5 cases (1.1%) found microbiological specimens not detected in previous bronchoscopy. None of them received antibiotics and evolved correctly. The potential total cost reduction during the study period at our centre if routine BA was deleted would be 21,937.50€ for routinely combined study. CONCLUSIONS: The low diagnostic yield of cytological and microbiological bronchial aspirate in EBUS-TBNA supports the idea of not performing routine BA. Although the potential for cost savings in caring for an individual patient is modest, many centres routinely perform BA, so the potential savings could be significant.

Impact of the COVID-19 pandemic on diagnosis of respiratory diseases in the Northern Metropolitan Area in Barcelona (Spain).

OBJECTIVE: The COVID-19 pandemic has had a great effect on the management of chronic diseases, by limiting the access to primary care and to diagnostic procedures, causing a decline in the incidence of most diseases. Our aim was to analyze the impact of the pandemic on primary care new diagnoses of respiratory diseases. METHODS: Observational retrospective study performed to describe the effect of COVID-19 pandemic on the incidence of respiratory diseases according to primary care codification. Incidence rate ratio between pre-pandemic and pandemic period was calculated. RESULTS: We found a decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications (J95). Instead, we found increases in flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). CONCLUSION: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic.

Incidence and Risk Factors for Infectious Complications of EBUS-TBNA: Prospective Multicenter Study.

The aim of our study was to describe the incidence of infectious complications of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) and to analyze the potential risk factors in a prospective cohort of patients. METHODS: We conducted a prospective multicenter study, with all consecutive patients referred for an EBUS-TBNA with patients at risk of developing an infectious complication (considering>10 nodal samplings, known immunosuppression, bronchial colonization and cavitated or necrotic lesions) and a second group without any risk factor. RESULTS: Three hundred seventy patients were included: 245 with risk factors and 125 without risk factors (as the control group). Overall, 15 patients (4.05%) presented an acute infectious complication: fourteen in cases (5.7%) and 1 in controls (0.8%). Of these, 4 patients presented pneumonia, 1 mediastinitis, 4 obstructive pneumonitis and 6 mild complications (respiratory tract infection that resolved with antibiotic). Also 7 (1.9%) patients had self-limited fever. One-month follow-up showed 1 mediastinitis at sixteenth day post-EBUS, which required surgical treatment, and 3 pneumonias and 3 respiratory tract infections at nineteenth day (1.9%). All patients had a good evolution and there were no deaths related with infectious complication. We observed an increased risk of complication in patients with risk factors and in patients with necrosis (p=0.018). CONCLUSIONS: The incidence of infectious complications in a subgroup of patients with risk factors was higher than in patients without risk factors. Nevertheless, it remains low, and no fatal complication occurred, which reinforces the idea that EBUS-TBNA is a safe technique for the assessment of the mediastinum. Necrotic lesions are a risk factor of post-EBUS infection, and their puncture should be avoided.

A novel intelligent radiomic analysis of perfusion SPECT/CT images to optimize pulmonary embolism diagnosis in COVID-19 patients.

BACKGROUND: COVID-19 infection, especially in cases with pneumonia, is associated with a high rate of pulmonary embolism (PE). In patients with contraindications for CT pulmonary angiography (CTPA) or non-diagnostic CTPA, perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) is a diagnostic alternative. The goal of this study is to develop a radiomic diagnostic system to detect PE based only on the analysis of Q-SPECT/CT scans. METHODS: This radiomic diagnostic system is based on a local analysis of Q-SPECT/CT volumes that includes both CT and Q-SPECT values for each volume point. We present a combined approach that uses radiomic features extracted from each scan as input into a fully connected classification neural network that optimizes a weighted cross-entropy loss trained to discriminate between three different types of image patterns (pixel sample level): healthy lungs (control group), PE and pneumonia. Four types of models using different configuration of parameters were tested. RESULTS: The proposed radiomic diagnostic system was trained on 20 patients (4,927 sets of samples of three types of image patterns) and validated in a group of 39 patients (4,410 sets of samples of three types of image patterns). In the training group, COVID-19 infection corresponded to 45% of the cases and 51.28% in the test group. In the test group, the best model for determining different types of image patterns with PE presented a sensitivity, specificity, positive predictive value and negative predictive value of 75.1%, 98.2%, 88.9% and 95.4%, respectively. The best model for detecting pneumonia presented a sensitivity, specificity, positive predictive value and negative predictive value of 94.1%, 93.6%, 85.2% and 97.6%, respectively. The area under the curve (AUC) was 0.92 for PE and 0.91 for pneumonia. When the results obtained at the pixel sample level are aggregated into regions of interest, the sensitivity of the PE increases to 85%, and all metrics improve for pneumonia. CONCLUSION: This radiomic diagnostic system was able to identify the different lung imaging patterns and is a first step toward a comprehensive intelligent radiomic system to optimize the diagnosis of PE by Q-SPECT/CT. HIGHLIGHTS: Artificial intelligence applied to Q-SPECT/CT is a diagnostic option in patients with contraindications to CTPA or a non-diagnostic test in times of COVID-19.

Bronchoscopy in Critically Ill COVID-19 Patients: Findings, Microbiological Profile, and Coinfection.

BACKGROUND: Bronchoscopy is a widely use technique in critically ill patients. Nosocomial coinfections are a cause of morbidity and mortality in intensive care units. OBJECTIVES: Our aim was to describe bronchoscopy findings and analyze microbiological profile and probably coinfection through bronchial aspirate (BA) samples in patients with coronavirus disease 2019 pneumonia requiring intensive care unit admission. METHODS: Retrospective observational study analyzing the BA samples collected from intubated patients with coronavirus disease 2019 in a referral Hospital (Spain). RESULTS: One hundred fifty-five consecutive BA samples were collected from 75 patients. Ninety (58%) were positive cultures for different microorganisms, 11 (7.1%) were polymicrobial, and 37 (23.7%) contained resistant microorganisms. There was a statistically significant association between increased days of orotracheal intubation and positive BA (18.9 vs. 10.9 d, P<0.01), polymicrobial infection (22.11 vs. 13.54, P<0.01) and isolation of resistant microorganisms (18.88 vs. 10.94, P<0.01). In 88% of the cases a new antibiotic or change in antibiotic treatment was made. CONCLUSION: Bronchoscopy in critically ill patient was safe and could be useful to manage these patients and conduct the microbiological study, that seems to be higher and different than in nonepidemic periods. The longer the intubation period, the greater the probability of coinfection, isolation of resistant microorganisms and polymicrobial infection.

No Effects of Meteorological Factors on the SARS-CoV-2 Infection Fatality Rate.

OBJECTIVE: Previous studies have shown that meteorological factors may increase COVID-19 mortality, likely due to the increased transmission of the virus. However, this could also be related to an increased infection fatality rate (IFR). We investigated the association between meteorological factors (temperature, humidity, solar irradiance, pressure, wind, precipitation, cloud coverage) and IFR across Spanish provinces ( n = 52) during the first wave of the pandemic (weeks 10-16 of 2020). METHODS: We estimated IFR as excess deaths (the gap between observed and expected deaths, considering COVID-19-unrelated deaths prevented by lockdown measures) divided by the number of infections (SARS-CoV-2 seropositive individuals plus excess deaths) and conducted Spearman correlations between meteorological factors and IFR across the provinces. RESULTS: We estimated 2,418,250 infections and 43,237 deaths. The IFR was 0.03% in < 50-year-old, 0.22% in 50-59-year-old, 0.9% in 60-69-year-old, 3.3% in 70-79-year-old, 12.6% in 80-89-year-old, and 26.5% in ≥ 90-year-old. We did not find statistically significant relationships between meteorological factors and adjusted IFR. However, we found strong relationships between low temperature and unadjusted IFR, likely due to Spain's colder provinces' aging population. CONCLUSION: The association between meteorological factors and adjusted COVID-19 IFR is unclear. Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses.

Predicting pulmonary embolism in patients infected with COVID-19 based on D-dimer levels and days between diagnosis of the infection and D-dimer determination.

Ruling out pulmonary embolism (PE) can be challenging in a situation of elevated D-dimer values such as in a case of COVID-19 infection. Our objective was to evaluate the difference in D-dimer values of subjects infected with COVID-19 in those with PE and those without and to analyze the predictive value of D-dimer for PE in these subjects based on the day of D-dimer determination. This was an observational, retrospective study, conducted at a tertiary hospital. All subjects with PCR-confirmed COVID-19 infection requiring hospital admission at our institution between the months of March and April 2020 were included in the study. We compared D-dimer levels in subjects who went on to develop a PE and those who did not. We then created a model to predict the subsequent development of a PE with the current D-dimer levels of the subject. D-dimer levels changed over time from COVID-19 diagnosis, but were always higher in subjects who went on to develop a PE. Regarding the predictive model created, the area under the curve of the ROC analyses of the cross-validation predictions was 0.72. The risk of pulmonary embolism for the same D-dimer levels varied depending on the number of days elapsed since COVID-19 diagnosis and D-dimer determination. To conclude, D-dimer levels were elevated in subjects with a COVID-19 infection, especially in those with PE. D-dimer levels increased during the first 10 days after the diagnosis of the infection and can be used to predict the risk of PE in COVID-19 subjects.

Rapid effect of benralizumab in exacerbation of severe eosinophilic asthma associated with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. CASE PRESENTATION: A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. CONCLUSIONS: The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.

[HOSPITALS AS PROMOTERS OF SMOKELESS SPACES: STRATEGIES AIMED AT SMOKING CONTROL] / El hospital como centro promotor de espacios sin humo: estrategias dirigidas al control del tabaquismo.

The objective of this study was to describe the measures introduced at the Hospital Germans Trias i Pujol, Barcelona, aimed at achieving a smoke-free environment, and encouraging research, training, and clinical approaches with respect to smoking. The experience gained as a center attached to the Catalan Network of Smokeless Hospitals since 2002 shows that preventing and controlling smoking requires a specific agenda developed by a competent committee comprising workers from all hospital areas. Likewise, coordination with other centers in the network is essential as it permits the sharing of experiences. The involvement of hospital management is critical for the effective introduction of health protection and promotion strategies, both in workers and in users. The raising of awareness and the ongoing training of all health workers and coordination with other health care providers in the Health network are the main aspects that require strengthening in the future.

El objetivo de este trabajo fue describir las medidas llevadas a cabo en el Hospital Germans Trias i Pujol de Barcelona, destinadas a conseguir un entorno libre de humo, así como al desarrollo de actividades de investigación, formación y abordaje clínico en relación al tabaquismo. La experiencia como centro adherido a la Red Catalana de Hospitales Sin Humo desde 2002 nos revela que para la prevención y control del tabaquismo es necesaria una agenda específica desarrollada por un Comité competente, compuesto por trabajadores de diferentes estamentos y servicios del centro. Del mismo modo, consideramos fundamental la coordinación con otros centros de la Red que permita compartir experiencias, así como la implicación de la Dirección del Centro para la implementación efectiva de las estrategias de promoción y protección de la salud, tanto en los trabajadores como en los usuarios. La sensibilización y formación continuada de todo el personal sanitario y la coordinación con otros servicios proveedores de salud de la red sanitaria se perfilan como los principales puntos a reforzar en el futuro.