Smokers and risk of hospital death by COVID calculated with SAVANA's natural language processing in the Castilla-La Mancha area.

INTRODUCTION: During the COVID pandemic, it was speculated that patients with the virus who were smoking-related might have a lower likelihood of disease exacerbation or death. To assess whether there is an association between smoking and risk of in-hospital mortality, SAVANA's big data and Natural Language Processing (NLP) technology is used. METHOD: A retrospective, observational, non-interventional cohort study was conducted based on real-life data extracted from medical records throughout Castilla La Mancha using Natural Language Processing and Artificial Intelligence techniques developed by SAVANA. The study covered the entire population of this region with Electronic Medical Records in SESCAM presenting with a diagnosis of COVID from March 1, 2020 to February 28, 2021. RESULTS: Smokers had a significantly higher percentage of cardiovascular risk factors (hypertension, dyslipidemia and diabetes), COPD, asthma, IDP, IC, CVD, PTE, cancer in general and lung cancer in particular, bronchiectasis, heart failure and a history of pneumonia (p < 0.0001).Former smokers, current smokers and non-smokers have a significant age difference. As for in-hospital deaths, they were more frequent in the case of ex-smokers, followed by smokers and then non-smokers (p < 0.0001). CONCLUSION: There is an increased risk of dying in hospital in SARS-COV2-infected patients who are active smokers or have smoked in the past.

Systemic Corticosteroids in Patients With Bronchial Asthma: A Real-Life Study

Objective: The objective of the present study was to determine the use of systemic corticosteroids (SCs) in patients with bronchial asthma using big data analysis. Methods: We performed an observational, retrospective, noninterventional study based on secondary data captured from free text in the electronic health records. This study was performed based on data from the regional health service of Castille-La Mancha (SESCAM), Spain. We performed the analysis using big data and artificial intelligence via Savana® Manager version 3.0. Results: During the study period, 103 667 patients were diagnosed with and treated for asthma at different care levels. The search was restricted to patients aged 10 to 90 years (mean age, 43.5 [95%CI, 43.4-43.7] years). Of these, 59.8% were women. SCs were taken for treatment of asthma by 58 745 patients t some point during the study period. These patients were older, with a higher prevalence of hypertension, dyslipidemia, diabetes, obesity, depression, and hiatus hernia. SCs are used frequently in the general population with asthma (31.4% in 2015 and 39.6% in 2019). SCs were prescribed mainly in primary care (59%), allergy (13%), and pulmonology (20%). The frequency of prescription of SCs had a direct impact on the main associated adverse effects. Conclusion: In clinical practice, SCs are frequently prescribed to patients with asthma, especially in primary care. Use of SCs is associated with a greater number of adverse events. It is necessary to implement measures to reduce prescription of SCs to patients with asthma, especially in primary care (AU)

Objetivo: El objetivo del presente estudio fue determinar el uso de corticoides sistémicos (CS) en pacientes con asma bronquial mediante el análisis de big data. Métodos: Se realizó un estudio observacional, retrospectivo y no intervencionista basado en datos secundarios capturados a partir de texto libre en las historias clínicas electrónicas. Este estudio se realizó a partir de los datos del Servicio Regional de Salud de Castilla-La Mancha (SESCAM), España. Se realizó el análisis mediante big data e inteligencia artificial a través de Savana® Manager versión 3.0. Resultados: Durante el periodo de estudio, 103 667 pacientes fueron diagnosticados y tratados de asma en los diferentes niveles asistenciales. La búsqueda se restringió a pacientes de entre 10 y 90 años (edad media, 43,5 [IC 95%, 43,4-43,7] años). De ellos, el 59,8% eran mujeres. 58 745 pacientes tomaron SC para el tratamiento del asma en algún momento del periodo de estudio. Estos pacientes eran de mayor edad, con una mayor prevalencia de hipertensión, dislipidemia, diabetes, obesidad, depresión y hernia de hiato. Los SC se utilizan con frecuencia en la población general con asma (31,4% en 2015 y 39,6% en 2019). Los SC se prescribieron principalmente en Atención Primaria (59%), Alergia (13%) y Neumología (20%). La frecuencia de prescripción de SCs tuvo un impacto directo en los principales efectos adversos asociados. Conclusiones: En la práctica clínica, los CS se prescriben con frecuencia a los pacientes con asma, especialmente en Atención Primaria. El uso de los CS se asocia a un mayor número de efectos adversos. Es necesario implementar medidas para reducir la prescripción de CS a los pacientes con asma, especialmente en Atención Primaria (AU)

N-acetylcysteine as a therapeutic approach to post-COVID-19 pulmonary fibrosis adjunctive treatment.

OBJECTIVE: Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis. MATERIALS AND METHODS: A search was performed in PubMed/MEDLINE. RESULTS: Interstitial changes have been observed in the CT scan of COVID-19 pneumonia. In patients with respiratory outcomes in the post-COVID-19 stage, glutathione (GSH) deficiency was found and interpreted as a reaction to the inflammatory cascade caused by the viral infection, while the pathophysiological process of pulmonary fibrosis involves numerous cytokines, such as TGF-ß, TNF-α, IL-1, PDGF and VEGF. NAC has a good tolerability profile, is easily administered orally and inexpensively, and has antioxidant and anti-inflammatory effects that may target the pathophysiologic mechanisms involved in pulmonary fibrosis. It may revert GSH deficiency, exerts direct and indirect antioxidant activity, anti-inflammatory activity and improves immune T-cell response. CONCLUSIONS: The mechanism of action of NAC suggests a role in the treatment of pulmonary fibrosis induced by COVID-19.

Systemic Corticosteroids in Patients with Bronchial Asthma: A Real-Life Study.

OBJECTIVES: The objective of the present study was to determine the use of systemic corti-costeroids (SCs) in patients with bronchial asthma using big data analysis. METHODS: We performed an observational, retrospective, noninterventional study based on secondary data captured from free text in the electronic health records. This study was per-formed based on data from the regional health service of Castille-La Mancha (SESCAM), Spain. We performed the analysis using big data and artificial intelligence via Savana® Manager version 3.0. RESULTS: During the study period, 103 667 patients were diagnosed with and treated for asthma at different care levels. The search was restricted to patients aged 10 to 90 years (mean age, 43.5 [95%CI, 43.4-43.7] years). Of these, 59.8% were women. SCs were taken for treatment of asthma by 58 745 patients at some point during the study period. These patients were older, with a higher prevalence of hypertension, dyslipidemia, diabetes, ob-esity, depression, and hiatus hernia. SCs are used frequently in the general population with asthma (31.4% in 2015 and 39.6% in 2019). SCs were prescribed mainly in primary care (59%), allergy (13%) and pulmonology (20%). The frequency of prescription of SCs had a direct impact on the main associated adverse effects. CONCLUSION: In clinical practice, SCs are frequently prescribed to patients with asthma, especially in primary care. Use of SCs is associated with a greater number of adverse events. It is necessary to implement measures to reduce prescription of SCs to patients with asthma, especially in primary care.

Roflumilast for COPD.

Patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis have a reduction in lung function and a higher risk of suffering exacerbations, which result in a deterioration in their quality of life, an accelerated progression of the disease and a greater mortality. COPD is currently considered an inflammatory disease involving airways and lung parenchyma. The symptoms that are typical of chronic bronchitis (chronic cough and sputum production) are markers of underlying inflammation, characteristic of COPD. Roflumilast, an antiinflammatory drug that belongs to the new therapeutic class of phosphodiesterase PDE4 inhibitors, is the first drug developed for the treatment of a specific phenotype of COPD (COPD associated with chronic bronchitis). The results of clinical trials indicated that in patients with COPD associated with chronic bronchitis and a history of exacerbations, roflumilast improves lung function and reduces the frequency of exacerbations that require medical interventions. This effect remained when it was added to a regular treatment with long-acting bronchodilators such as tiotropium or long-acting ß2-adrenoceptor agonists (LABAs) such as salmeterol. Roflumilast has been shown to be generally well tolerated. Side effects were typically mild to moderate and included diarrhea, nausea, weight decrease and headache. Gastrointestinal side effects mainly occurred within the first weeks of therapy and mostly resolved on continued treatment.

Study of the burden on patients with chronic obstructive pulmonary disease.

BACKGROUND: Health-related quality of life measures are widely used in patients with chronic obstructive pulmonary disease (COPD). However, they are extremely limited when used to evaluate patients outside the clinical trials. The aim of this study was to analyse the burden of the disease using a simple, validated, self-administered questionnaire specifically developed for patients in daily clinical practice. METHODS: A total of 3935 patients (74.5% men; mean age, 67 years) participated in a cross-sectional study. The burden of COPD on patients was measured using the Clinical COPD Questionnaire (CCQ). COPD was rated at four levels by the forced expiratory volume in one second (FEV(1)) according to The Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale. RESULTS: The disease mainly affects old men (more than 50% were over 65 years of age) and non-employed men (23% were employed). Of the patients studied, 22.7% continued smoking, especially men (24.4% of men vs. 18.1% of women). Most patients (54%) were diagnosed with moderate stage II COPD. Severity of COPD was lower in women: 29.6% of men had severe COPD compared with 13.7% of women. During the last year, 65.1% had at least one acute exacerbation and 36.6% were admitted to hospital because of COPD exacerbation. No association was found between the body mass index and COPD stage. The variable that most influenced the disease burden was dyspnoea, as progression from grade 0 to grade 4 increased the disease burden by 1.78 points for symptoms, 2.43 for functional state and 1.53 for mental state. The functional classification of COPD also had a significant influence on the disease burden. CONCLUSIONS: The present findings show that dyspnoea and the degree of airflow limitation are the clinical variables that most affect the burden of COPD from the patient's point of view.

Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma.

BACKGROUND: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.

The burden of COPD in Spain: results from the Confronting COPD survey.

Chronic obstructive pulmonary disease is a smoking-related condition of progressive airflow obstruction, with disabling symptoms of chronic dyspnoea, cough and sputum production. In Spain, as in other countries worldwide, only a limited number of studies have attempted to quantify the impact of COPD on the patient, healthcare system and society. To obtain comprehensive information about the burden of this disease, an economic analysis of a large international survey, Confronting COPD in North America and Europe, was conducted. The results of the economic analysis of data from the Spanish survey sample estimated that the annual cost of COPD to the healthcare system was Euro 3238 per patient, with indirect costs amounting to Euro 300 per patient bringing the total societal cost of the disease to Euro 3538 per patient per year. A significant proportion of the economic burden of COPD on the Spanish healthcare system was associated with inpatient hospitalization (Euro 2708), which accounted for almost 84% of the total direct cost of the disease. As the major cause of inpatient hospitalization for COPD is acute exacerbations, these results highlight the need for interventions in the outpatient setting to prevent exacerbations in Spain. The impact of COPD on the healthcare system may also be due to the underdiagnosis and treatment of COPD, suggesting that costs may be reduced by improving the diagnosis and treatment of the disease in primary care. The sub-analysis of costs from the survey showed that patients with severe COPD were associated with considerably higher total societal costs than patients with mild disease (Euro 9850 versus Euro 1316 per patient). Therefore, introducing interventions to reduce the progression to severe COPD could also reduce the impact of the disease.

Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.

The objective of the present trial was to compare the efficacy, safety, and tolerability of moxifloxacin (400 mg) given intravenously (i.v.) once daily followed by oral moxifloxacin (400 mg) for 7 to 14 days with the efficacy, safety, and tolerability of co-amoxiclav (1.2 g) administered by i.v. infusion three times a day followed by oral co-amoxiclav (625 mg) three times a day, with or without clarithromycin (500 mg) twice daily (i.v. or orally), for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy. A total of 628 patients were enrolled and assessed by evaluation of their clinical and bacteriological responses 5 to 7 days and 21 to 28 days after administration of the last dose of study medication. Although the trial was designed, on the basis of predefined outcomes, to demonstrate the equivalence of the two regimens, the results showed statistically significant higher clinical success rates (for moxifloxacin, 93.4%, and for comparator regimen, 85.4%; difference [Delta], 8.05%; 95% confidence interval [CI], 2.91 to 13.19%; P = 0.004) and bacteriological success rates (for moxifloxacin, 93.7%, and for comparator regimen, 81.7%; Delta, 12.06%; 95% CI, 1.21 to 22.91%) for patients treated with moxifloxacin. This superiority was seen irrespective of the severity of the pneumonia and whether or not the combination therapy included a macrolide. The time to resolution of fever was also statistically significantly faster for patients who received moxifloxacin (median time, 2 versus 3 days), and the duration of hospital admission was approximately 1 day less for patients who received moxifloxacin. The treatment was converted to oral therapy immediately after the initial mandatory 3-day period of i.v. administration for a larger proportion of patients in the moxifloxacin group than patients in the comparator group (151 [50.2%] versus 57 [17.8%] patients). There were fewer deaths (9 [3.0%] versus 17 [5.3%]) and fewer serious adverse events (38 [12.6%] versus 53 [16.5%]) in the moxifloxacin group than in the comparator group. The rates of drug-related adverse events were comparable in both groups (38.9% in each treatment group). The overall incidence of laboratory abnormalities was similar in both groups. Thus, it is concluded that monotherapy with moxifloxacin is superior to that with a standard combination regimen of a beta-lactam and a beta-lactamase inhibitor, co-amoxiclav, with or without a macrolide, clarithromycin, in the treatment of patients with community-acquired pneumonia admitted to a hospital.

Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón).

We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferón) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation was not mediated by an increase in CD3(-)CD56(+) NK cells. Further, glycophosphopeptical significantly increased the percentage of monocytes and PMNs that phagocytize Escherichia coli in vitro, as well as increased phagocytic indices. We conclude that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.

Extent of centrilobular and panacinar emphysema in smokers' lungs: pathological and mechanical implications.

In order to quantify the extent of centrilobular (CLE) and panacinar (PLE) emphysema and the degree of the possible overlap between the two forms in smokers, the lungs of 25 smokers undergoing lung resection for peripheral lung tumours were studied. The extent of CLE and PLE was assessed by point counting, and the lungs were classified as having pure CLE (C, n = 5), predominant CLE with areas of PLE (CP, n = 7), predominant PLE with features of CLE (PC, n = 7), and pure PLE (P, n = 6) according to the percentage of lung involved by either form. Preoperative pulmonary function tests and the score of inflammation and the diameters of the small airways were also measured. Mean linear intercept (Lm), a measure of mean interalveolar wall distances and forced expiratory volume in one second (FEV1) were similar in the four groups. Small airway pathology was a predominant feature in lungs with CLE, and was significantly decreased in a stepwise fashion as the amount of PLE increased. This was especially so for the amount of muscle in the airway wall and the diameters of the airways. By contrast, lung compliance was higher in panacinar than in centrilobular emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)

Centrilobular and panlobular emphysema in smokers. Two distinct morphologic and functional entities.

In order to investigate the hypothesis that different morphologic patterns of disease might correspond to different mechanical properties of the lung in emphysema, pulmonary function tests and lung mechanics were measured in 34 subjects undergoing lung resection for peripheral lung tumors. Using standard microscopic criteria, pure or predominant centrilobular (n = 18) or panlobular (n = 16) emphysema was diagnosed in lungs. The degree of emphysema measured by the mean linear intercept (Lm) was not significantly different between the two groups. However, the coefficient of variation of the interalveolar wall distance (CV) was significantly higher for the same Lm in CLE than in PLE. This indicates that CLE has an uneven pattern of destruction, whereas PLE is more homogeneous. CLE had a higher degree of abnormalities in the small airways (SAD) than did PLE (p less than 0.05) mainly because of significantly higher muscle score (p less than 0.001) and fibrosis. CLE also had a higher proportion of airways less than 400 microns in diameter than did PLE (p less than 0.05). Static compliance, specific compliance, and the exponential constant (K) were significantly lower (p less than 0.005, p less than 0.001, and p less than 0.05, respectively) in CLE than in PLE. FEV1/FVC was significantly correlated with SAD in CLE (r = -0.69, p less than 0.01) but not in PLE (r = 0.29 p greater than 0.05); conversely, FEV1/FVC was significantly correlated with elasticity (K) in PLE (r = -0.72, p less than 0.01) but not in CLE (r = 0.08, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)