Basic host response parameters to classify mortality risk in COVID-19 and community-acquired pneumonia.

Improved phenotyping in pneumonia is necessary to strengthen risk assessment. Via a feasible and multidimensional approach with basic parameters, we aimed to evaluate the effect of host response at admission on severity stratification in COVID-19 and community-acquired pneumonia (CAP). Three COVID-19 and one CAP multicenter cohorts including hospitalized patients were recruited. Three easily available variables reflecting different pathophysiologic mechanisms-immune, inflammation, and respiratory-were selected (absolute lymphocyte count [ALC], C-reactive protein [CRP] and, SpO2/FiO2). In-hospital mortality and intensive care unit (ICU) admission were analyzed as outcomes. A multivariable, penalized maximum likelihood logistic regression was performed with ALC (< 724 lymphocytes/mm3), CRP (> 60 mg/L), and, SpO2/FiO2 (< 450). A total of 1452, 1222 and 462 patients were included in the three COVID-19 and 1292 in the CAP cohort for the analysis. Mortality ranged between 4 and 32% (0 to 3 abnormal biomarkers) and 0-9% in SARS-CoV-2 pneumonia and CAP, respectively. In the first COVID-19 cohort, adjusted for age and sex, we observed an increased odds ratio for in-hospital mortality in COVID-19 with elevated biomarkers altered (OR 1.8, 3, and 6.3 with 1, 2, and 3 abnormal biomarkers, respectively). The model had an AUROC of 0.83. Comparable findings were found for ICU admission, with an AUROC of 0.76. These results were confirmed in the other COVID-19 cohorts Similar OR trends were reported in the CAP cohort; however, results were not statistically significant. Assessing the host response via accessible biomarkers is a simple and rapidly applicable approach for pneumonia.

Bronchiectasis not due to cystic fibrosis. / Bronquiectasias no debidas a fibrosis quística.

Bronchiectasis is a clinical-radiological condition composed of irreversible bronchial dilation due to inflammation and infection of the airways, which causes respiratory symptoms, usually productive cough and infectious exacerbations. Bronchiectasis can have multiple causes, both pulmonary and extrapulmonary, and its clinical presentation is very heterogenous. Its prevalence is unknown, although up to 35-50% of severe COPD and 25% of severe asthma present them, so their underdiagnosis is evident. Chronic bacterial bronchial infection is common, and Pseudomonas aeruginosa is the pathogen that has been found to imply a worse prognosis. Treatment of bronchiectasis has three fundamental characteristics: it must be multidisciplinary (involvement of several specialties), pyramidal (from primary care to the most specialized units) and multidimensional (management of all aspects that make up the disease).

Influence of physical activity on the prognosis of COPD patients: the HADO.2 score - health, activity, dyspnoea and obstruction.

Objective: The aim of this study was to create a prognostic instrument for COPD with a multidimensional perspective that includes physical activity (PA). The score also included health status, dyspnoea and forced expiratory volume in 1 s (HADO.2 score). Methods: A prospective, observational, non-intervention study was carried out. Patients were recruited from the six outpatient clinics of the respiratory service of a single university hospital. The component variables of the HADO.2 score and BODE index were studied, and PA was measured using an accelerometer. The outcomes for the HADO.2 score were mortality and hospitalisations during follow-up and an exploration of the correlation with health-related quality of life at the moment of inclusion in the study. Results: 401 patients were included in the study and followed up for three years. The HADO.2 score showed good predictive capacity for mortality: C-index 0.79 (0.72-0.85). The C-index for hospitalisations was 0.72 (0.66-0.77) and the predictive ability for quality of life, as measured by R2, was 0.63 and 0.53 respectively for the Saint George's Respiratory Questionnaire and COPD Assessment Test. Conclusions: There was no statistically significant difference between the mortality predictive capacity of the HADO.2 score and the BODE index. Adding PA to the original BODE index significantly improved the predictive capacity of the index. The HADO.2 score, which includes PA as a key variable, showed good predictive capacity for mortality and hospitalisations. There were no differences in the predictive capacity of the HADO.2 score and the BODE index.

Abordaje paliativo en enfermedades respiratorias avanzadas / Palliative Approach in Advanced Respiratory Diseases

Las enfermedades respiratorias crónicas avanzadas son prevalentes y producen deterioro de la calidad de vida, en particular la enfermedad pulmonar obstructiva crónica (EPOC), las enfermedades pulmonares intersticiales difusas (EPID) y las enfermedades neuromusculares progresivas con compromiso diafragmático (ENM). Quienes las padecen presentan síntomas persistentes que no son siempre adecuada-mente controlados por los tratamientos recomendados por las guías clínicas de mane-jo. El tratamiento paliativo de los síntomas persistentes es un punto relevante y suelen presentarse barreras para su implementación.Este artículo ofrece una revisión narrativa sobre una perspectiva latinoamericana acerca del rol de los cuidados paliativos en enfermedades respiratorias avanzadas.

Advanced chronic respiratory diseases are prevalent and cause deterioration in qual-ity of life, particularly chronic obstructive pulmonary disease (COPD), diffuse intersti-tial lung diseases (ILD) and progressive neuromuscular diseases with diaphragmatic involvement (NMD). Those who suffer from them usually present persistent symptoms that are not always adequately controlled by the treatments recommended by the clinical management guidelines. Palliative treatment of persistent symptoms is a relevant point, but the pal-liative approach usually presents barriers to its implementation.This article offers a narrative review over Latin American perspective on the role of pal-liative care in advanced respiratory diseases.

Efficacy and Safety of Dry Powder Antibiotics: A Narrative Review.

The use of inhaled antibiotics was initially almost exclusively confined to patients with cystic fibrosis (CF). However, it has been extended in recent decades to patients with non-CF bronchiectasis or chronic obstructive pulmonary disease who present with chronic bronchial infection by potentially pathogenic microorganisms. Inhaled antibiotics reach high concentrations in the area of infection, which enhances their effect and enables their long-term administration to defeat the most resistant infections, while minimizing possible adverse effects. New formulations of inhaled dry powder antibiotics have been developed, providing, among other advantages, faster preparation and administration of the drug, as well as avoiding the requirement to clean nebulization equipment. In this review, we analyze the advantages and disadvantages of the different types of devices that allow the inhalation of antibiotics, especially dry powder inhalers. We describe their general characteristics, the different inhalers on the market and the proper way to use them. We analyze the factors that influence the way in which the dry powder drug reaches the lower airways, as well as aspects of microbiological effectiveness and risks of resistance development. We review the scientific evidence on the use of colistin and tobramycin with this type of device, both in patients with CF and with non-CF bronchiectasis. Finally, we discuss the literature on the development of new dry powder antibiotics.

The role of precision medicine in bronchiectasis: emerging data and clinical implications.

INTRODUCTION: Bronchiectasis is a very heterogeneous disease. This heterogeneity has several consequences: severity cannot be measured by a single variable, so multidimensional scores have been developed to capture it more broadly. Some groups of patients with similar clinical characteristics or prognoses (clinical phenotypes), and even similar inflammatory profiles (endotypes), have been identified, and these have been shown to require a more specific treatment. AREAS COVERED: We comment on this 'stratified' model of medicine as an intermediate step toward the application of the usual concepts on which precision medicine is based (such as cellular, molecular or genetic biomarkers, treatable traits and individual clinical fingerprinting), whereby each subject presents certain specific characteristics and receives individualized treatment. EXPERT OPINION: True precision or personalized medicine is based on concepts that have not yet been fully achieved in bronchiectasis, although some authors are already beginning to adapt them to this disease in terms of pulmonary and extrapulmonary etiologies, clinical fingerprinting (specific to each individual), cellular biomarkers such as neutrophils and eosinophils (in peripheral blood) and molecular biomarkers such as neutrophil elastase. In therapeutic terms, the future is promising, and some molecules with significant antibiotic and anti-inflammatory properties are being developed.

Early Desaturation During 6-Minute Walk Test is a Predictor of Mortality in COPD.

BACKGROUND: Oxygen desaturation during exercise is mainly observed in severe cases of chronic obstructive pulmonary disease (COPD) and is associated with a worse prognosis, but little is known about the type of desaturation that causes the greatest risk of mortality. MATERIAL AND METHODS: We studied all of the 6-min walk tests performed periodically at a tertiary hospital over a period of 12 years in patients with moderate or severe COPD. We classified patients as non-desaturators if they did not suffer a drop in oxygen saturation (SpO2 < 88%) during the test, early desaturators if the time until desaturation was < 1 min, and non-early desaturators if it was longer than 1 min. The average length of follow-up per patient was 5.6 years. RESULTS: Of the 319 patients analyzed, 126 non-desaturators, 91 non-early desaturators and 102 early desaturators were identified. The mortality analysis showed that early desaturators had a mortality of 73%, while it was 38% for non-early desaturators and 28% for non-desaturators, with a survival of 5.9 years compared to 7.5 years and 9.6 years, respectively (hazard ratio of 3.50; 95% CI 2.3-5.3; p < 0.0001). CONCLUSIONS: The early desaturation seen in patients with chronic obstructive pulmonary disease is associated with greater mortality and is likely responsible for the poor prognosis shown globally in patients who desaturate. The survival of patients with early desaturation is almost 4 years less with respect to non-desaturators, and they, thus, require closer observation.

The U-Shaped Relationship Between Eosinophil Count and Bronchiectasis Severity: The Effect of Inhaled Corticosteroids.

BACKGROUND: Although a proven relationship exists between the blood eosinophil count (BEC) and the severity of both asthma and COPD, its relationship with bronchiectasis has not been well established. The objective of this study was to analyze the relationship between BEC and the number and severity of exacerbations, and patients' responses to inhaled corticosteroid (IC) treatment in bronchiectasis RESEARCH QUESTION: Does an association exist among BEC, the number of exacerbations and severity of bronchiectasis, and IC treatment? STUDY DESIGN AND METHODS: This was a multicenter (43 centers) prospective observational study derived from the Spanish Bronchiectasis Registry. Patients with proven bronchiectasis and a known BEC were included, whereas those with asthma or antieosinophilic treatments were excluded. Patients were divided into four groups according to the BEC at the time of inclusion in the study in a steady-state situation: (1) eosinopenic bronchiectasis (< 50 eosinophils/µL), (2) low number of eosinophils (51-100/µL), (3) normal number of eosinophils (101-300/µL), and (4) eosinophilic bronchiectasis (> 300 eosinophils/µL). RESULTS: Nine hundred twenty-eight patients finally were included: 123 patients (13.3%) with < 50 eosinophils/µL (eosinopenic group), 164 patients (17.7%) with 50-100 eosinophils/µL, 488 patients (52.6%) with 101-300 eosinophils/µL, and 153 patients (16.5%) with > 300 eosinophils/µL (eosinophilic group). BEC showed a significant U-shaped relationship with severity, exacerbations, lung function, microbiologic profile, and IC treatment (these being higher in the eosinopenic group compared with the eosinophilic group). IC treatment significantly decreased the number and severity of exacerbations only in the group of bronchiectasis patients with > 300 eosinophils/µL. INTERPRETATION: A significant U-shaped relationship was found between BEC and severity and exacerbations in bronchiectasis that was more pronounced in the eosinopenic group. IC treatment decreased the number and severity of exacerbations only in the eosinophilic group.

Inhaled Colistimethate Sodium in the Management of Patients with Bronchiectasis Infected by Pseudomonas aeruginosa: A Narrative Review of Current Evidence.

International guidelines on the treatment of bronchiectasis indicate that the use of inhaled antibiotics is effective, especially in symptomatic chronic bronchial infection (CBI) due to Pseudomonas aeruginosa (PA). To date, however, no such treatment has been approved by regulatory agencies. Of the inhaled antibiotics on the market, colistimethate sodium (colistin) is one of the most used in many countries, either in its nebulized presentation or as dry powder. Among the characteristics of this antibiotic, it is worth noting that its main target is the lipopolysaccharide in the outer membrane of the cell wall of gram-negative bacteria and that it has a low rate of resistance to PA (<1%). Most observational studies have shown that the use of colistin in patients with bronchiectasis and CBI due to PA results in a decrease in both the number and severity of exacerbations, an improvement in quality of life, a decrease in sputum volume and purulence, and a high rate of PA eradication, although there are no clear differences with respect to other inhaled antibiotics. However, the lack of randomized clinical trials (RCT) with positive results for its main variable (exacerbations) in an intention-to-treat analysis has prevented its approval by regulatory agencies as a formal indication for use in bronchiectasis. The PROMIS program, made up of two RCT with identical methodology, is currently underway. The first of these RCT (already concluded) has demonstrated a clearly positive effect on the group randomized to colistin in its main variable (number of annual exacerbations), while the results of the second are still pending. This review presents exhaustive information on the pharmacological and microbiological characteristics of colistin, the results of the studies carried out to date, and the future challenges associated with this treatment.

Incidence and profile of severe exacerbations of chronic obstructive pulmonary disease due to biomass smoke or tobacco.

INTRODUCTION AND OBJECTIVES: Stable chronic obstructive pulmonary disease (COPD) caused by biomass smoke (B-COPD) has some differences from tobacco-induced-COPD (T-COPD), but acute exacerbations (AECOPD) have not been well characterized in B-COPD. OBJECTIVE: To compare the incidence, characteristics and outcomes of AECOPD in B-COPD with those of T-COPD. METHODS: A retrospective observational study that included consecutive patients seen at a specialized COPD clinic (2008-2021). The incidence of severe AECOPD that required hospital admission was studied. For the first AECOPD, the following variables were recorded: fever, coexistence of pneumonia, purulent sputum, eosinophil count, neutrophil to lymphocyte ratio, hypercapnia, and respiratory acidosis. Outcome variables were intensive care unit (ICU) admission, length of hospital stay, and mortality within 1 month of hospital admission. RESULTS: Of 1060 subjects, 195 (18.4%) belonged to the B-COPD group and 865 (81.6%) to the T-COPD group. During a follow-up of 67.9 (37.8-98.8) months, 75 (38.4%) patients in the B-COPD group and 319 (36.8%) in the T-COPD group suffered at least one severe AECOPD. The only difference between groups was in a higher risk of ICU admission for the T-COPD group. The incidence, characteristics, and the rest of the outcomes of AECOPD were similar for both groups. CONCLUSION: AECOPD are similar events for B-COPD and T-COPD and should be managed similarly.

Peripheral Neutrophil-to-Lymphocyte Ratio in Bronchiectasis: A Marker of Disease Severity.

Most patients with bronchiectasis have a predominantly neutrophilic inflammatory profile, although other cells such as lymphocytes (as controllers of bronchial inflammation) and eosinophils also play a significant pathophysiological role. Easy-to-interpret blood biomarkers with a discriminative capacity for severity or prognosis are needed. The objective of this study was to assess whether the peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with different outcomes of severity in bronchiectasis. A total of 1369 patients with bronchiectasis from the Spanish Registry of Bronchiectasis were included. To compare groups, the sample was divided into increasing quartiles of NLR ratio. Correlations between quantitative variables were established using Pearson's P test. A simple linear regression (with the value of exacerbations as a quantitative variable) was used to determine the independent relationship between the number and severity of exacerbations and the NLR ratio. The area under the curve (AUC)-ROC was used to determine the predictive capacity of the NLR for severe bronchiectasis, according to the different multidimensional scores. Mean age: 69 (15) years (66.3% of women). The mean NLR was 2.92 (2.03). A higher NLR was associated with more severe bronchiectasis (with an especially significant discriminative power for severe forms) according to the commonly used scores (FACED, E-FACED and BSI), as well as with poorer quality of life (SGRQ), more comorbidities (Charlson index), infection by pathogenic microorganisms, and greater application of treatment. Furthermore, the NLR correlated better with severity scores than other parameters of systemic inflammation. Finally, it was an independent predictor of the incident number and severity of exacerbations. In conclusion, the NLR is an inexpensive and easy-to-measure marker of systemic inflammation for determining severity and predicting exacerbations (especially the most severe) in patients with bronchiectasis.