Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent.

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3-6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3'-dione were found altered in PRE, and their levels returned to those of a baseline control group 3-6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.

COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients.

BACKGROUND: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. METHODS: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. RESULTS: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. CONCLUSION: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.

Step-Up and Step-Down Treatment Approaches for COPD: A Holistic View of Progressive Therapies.

Recent advances in inhaled drugs and a clearer definition of the disease have made the task of managing COPD more complex. Different proposals have been put forward which combine all the available treatments and the different clinical presentations in an effort to select the best therapeutic options for each clinical context. As COPD is a chronic progressive disease, the escalation of therapy has traditionally been considered the most natural way to tackle it. However, the notion of COPD as a constantly progressing disease has recently been challenged and, in specific areas, this points to the possibility of a de-escalation in treatment. In this context, the clinician requires simple, specific recommendations to guide these changes in treatment in their daily clinical practice. To accomplish this, the first step must be a correct evaluation and an accurate initial preliminary diagnosis of the patient's condition. Thereafter, the first escalation in therapy must be introduced with caution as the disease progresses, since clinical trials are not designed with clinical decision-making in mind. During this escalation, three possibilities are open to change the current treatment for a different one within the same family, to increase non-pharmacological interventions or to increase the pharmacological therapies. Beyond that point, a patient with persistent symptoms represents a complex clinical scenario which requires a specialized approach, including the evaluation of different respiratory and non-respiratory comorbidities. Unfortunately, there are few de-escalation studies available, and these are mainly observational in nature. The debate on de-escalation in pharmacological treatment, therefore, involves two main discussion points: the withdrawal of bronchodilators and the withdrawal of inhaled steroids. Altogether, the scheme for modifying treatment must be more personalized than just adding molecules, and the therapeutic response and its conditioning factors should be evaluated at each step before proceeding further.

A Delphi Consensus Document on the Use of Single-Inhaler Fixed-Dose Triple Therapies in COPD Patients.

Introduction: Despite the evidence provided by clinical trials, there are some uncertainties and controversies regarding the use of triple inhaled therapy. With the aim of evaluating clinical practice in specialized respiratory units, a Delphi consensus document was implemented on the use of single-inhaler fixed-dose triple therapies after 1 year of use in Spain. Methods: A scientific committee of COPD experts defined a thematic index, guided a systematic literature review and helped design the Delphi questionnaire. This was sent to the other 45 COPD experts between April and June 2019. Agreement/disagreement on 58 statements was tested in two rounds using a Likert scale. Replies were classified as a consensus when ≥80% of the panelists agreed; a majority when a degree of agreement of ≥66% was reached; and divergence if agreement was <66%. Results: After two rounds, 44.44% of the statements reached consensus, 14.81% reached majority and 40.74% were divergent. Panelists agreed that escalating from double bronchodilation should be phenotype-based and aim to prevent exacerbations but not for improving symptoms. The addition of an antimuscarinic to inhaled corticosteroids combinations achieves improvement in lung function, symptoms and exacerbation prevention. Main safety concerns included the increased risk of pneumonia as compared to bronchodilator therapies, with similar cardiovascular effects. There was no consensus agreement on patient type response based on blood eosinophil counts or obstruction severity. Conclusion: The low degree of consensus among panelists may reflect the complexity of severe COPD management. The information provided here may be useful to clinicians implementing personalized medicine for COPD patients.

The clinical implications of triple therapy in fixed-dose combination in COPD: from the trial to the patient.

The emergence of a fixed-dose combination (FDC) of a long-acting ß2-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled corticosteroid (ICS) in a single inhalation device has changed the approach to inhaled therapy. Although clinical trials describe the efficacy and safety of these FDCs, their use in daily clinical practice can present challenges for the clinician in two specific scenarios. In patients who are already receiving triple therapy via different devices, switching to FDCs could confer benefits by reducing critical errors in the management of inhalers, improving therapeutic adherence, and lowering costs, while maintaining the same clinical efficacy. In patients who are not receiving triple therapy in different devices and who require a change in treatment, triple therapy FDC has shown benefits in clinical trials. Although methodological differences among the trials advise against direct comparison, clinical results show good efficacy, but also considerable variability, and a number of clinical outcomes have yet to be explored. In the future, trials must be developed to complete clinical efficacy data. Real-world efficacy trials are needed, and studies must be designed to determine the profile of patients who present a greater therapeutic response to each FDC in order to pave the way towards more personalized treatment.

Medical Care According to Risk Level and Adaptation to Spanish COPD Guidelines (Gesepoc): The Epoconsul Study. / Atención médica según el nivel de riesgo y su adecuación a las recomendaciones de la guía española de la enfermedad pulmonar obstructiva crónica (EPOC) (GesEPOC): Estudio EPOCONSUL.

INTRODUCTION: EPOCONSUL is the first national audit to analyze medical care for COPD in pulmonology departments in Spain. The main objective was to perform a retrospective analysis to determine the distribution of GesEPOC 2017 COPD risk levels and to evaluate clinical activity according to the new recommendations. MATERIAL AND METHODS: This is a cross-sectional clinical audit in which consecutive COPD cases were recruited over one year. The study evaluated risk and clinical phenotype according to GesEPOC 2017, and their correlation with the clinical interventions employed. RESULTS: The most common risk category was high risk (79.8% versus 20.2%; p < 0.001), characterized by a higher level of severity on BODE and BODEx indexes, and a higher comorbidity burden. The most common phenotype was non-exacerbator. The most commonly used treatment in low-risk patients was bronchodilator monotherapy (34.8%) and triple therapy in high-risk patients (53.7%). High risk was most frequently characterized by phenotype (57.6% versus 52%; p = 0.014) and pulmonary function test results: lung volume (47.7% versus 35.8%; p < 0.001), lung diffusion (51.4% versus 42.1%; p < 0.001) and walk test (37.8% versus 15.8%; p < 0.001). CONCLUSIONS: Most patients treated in pulmonology departments were high-risk and non-exacerbator phenotype. Clinical interventions differed according to risk level and mainly followed GesEPOC recommendations, although there is significant room for improvement.

How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting ß2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.