Prepandemic viral community-acquired pneumonia: Diagnostic sensitivity and specificity of nasopharyngeal swabs and performance of clinical severity scores.

The objectives of this work were to assess the diagnostic sensitivity and specificity of nasopharyngeal (NP) swabs for viral community-acquired pneumonia (CAP) and the performance of pneumonia severity index (PSI) and CURB-65 severity scores in the viral CAP in adults. A prospective observational cohort study of consecutive 341 hospitalized adults with CAP was performed between January 2018 and March 2020. Demographics, comorbidities, symptoms/signs, analytical data, severity scores, antimicrobials, and outcomes were recorded. Blood, NP swabs, sputum, and urine samples were collected at admission and assayed by multiplex real time-PCR, bacterial cultures, and Streptococcus pneumoniae and Legionella pneumophila antigens detection, to determine the etiologies and quantify the viral load. The etiology was identified in 174 (51.0%) patients, and in 85 (24.9%) it was viral, the most frequent rhinovirus and influenza virus. The sensitivity of viral detection in sputum (50.7%) was higher than in NP swabs (20.9%). Compared with sputum, the positive predictive value and specificity of NP swabs for viral diagnosis were 95.8% and 96.9%, respectively. Performance of PSI and CURB-65 scores in all CAP with etiologic diagnosis were as expected, with mortality associated with higher values, but they were not associated with mortality in patients with viral pneumonia. NP swabs have lower sensitivity but high specificity for the diagnosis of viral CAP in adults compared with sputum, reinforcing the use NP swabs for the diagnostic etiology work-up. The PSI and CURB-65 scores did not predict mortality in the viral CAP, suggesting that they need to be updated scores based on the identification of the etiological agent.

Outpatient Parenteral Antimicrobial Treatment for Non-Cystic Fibrosis Bronchiectasis Exacerbations: A Prospective Multicentre Observational Cohort Study.

BACKGROUND: The recently published guidelines of the Spanish Society of Pulmonology and Thoracic Surgery encourage physicians to use outpatient antimicrobial therapy to treat exacerbations in patients with non-cystic fibrosis bronchiectasis (NCFB). The published literature on this topic, however, is scarce. METHODS: We report a prospective observational cohort study of patients with NCFB who received treatment at home for at least one exacerbation episode between September 2012 and September 2017 as part of an outpatient parenteral antimicrobial therapy (OPAT) program. Patients were included in the analysis if they fulfilled all of the following criteria: established diagnosis of bronchiectasis according to current guidelines criteria, clinical exacerbation, requiring intravenous antibiotics because of failure to respond to oral antibiotics, or isolation of a microorganism resistant to oral options. OBJECTIVES: To evaluate the effectiveness and safety of the treatment of patients with NCFB exacerbations in an OPAT program under "real-world" conditions. RESULTS: Sixty-seven patients were treated in the OPAT program due to bacterial exacerbations of NCFB. Forty-five (67.2%) patients were admitted to hospital for a median of 7 days before starting OPAT. Sixty-three (94%) patients achieved resolution of the exacerbation at the end of therapy. Four patients needed hospital readmission, and one died. The OPAT program saved 11,586 days of hospital admission, equivalent to EUR 7,866,904. CONCLUSIONS: OPAT appears to be a safe, effective, and efficient strategy for treating patients with exacerbations of NCFB.

Ten Research Questions for Improving COPD Care in the Next Decade.

With the 60th anniversary of the CIBA symposium, it is worth evaluating research questions that should be prioritized in the future. Coming research initiatives can be summarized in 10 main areas. (1) From epidemiology the impact of new forms of electronic cigarettes on prevalence and mortality of COPD will be sought. (2) The study of the disease endotypes and its relationship phenotypes will have to be unraveled in the next decade. (3) Diagnosis of COPD faces several challenges opening the possibility of a change in the definition of the disease itself. (4) Patients' classification and risk stratification will need to be clarified and reassessed. (5) The asthma-COPD overlap dilemma will have to be clarified and define whether both conditions represent one only chronic airway disease again. (6) Integrating comorbidities in COPD care will be key in a progressively ageing population to improve clinical care in a chronic care model. (7) Nonpharmacological management have areas for research including pulmonary rehabilitation and vaccines. (8) Improving physical activity should focus research because of the clear prognostic impact. (9). Pharmacological therapies present several challenges including efficacy and safety issues with current medications and the development of biological therapy. (10) The definition, identification, categorization and specific therapy of exacerbations will also be an area of research development. During the next decade, we have a window of opportunity to address these research questions that will put us on the path for precision medicine.

Current controversies in the stepping up and stepping down of inhaled therapies for COPD at the patient level.

The implementation of potential new step-up or step-down treatment recommendations in response to current guidelines is one of the main challenges currently faced in actual daily practice settings. In the present narrative review, we aim to discuss the relevance of these step-up and step-down proposals at the patient level in daily clinical practice. In particular, we aim to review the challenges associated with inhaled maintenance therapy for chronic obstructive pulmonary disease (COPD) in four clinical scenarios. First, we discuss the step up from single to double bronchodilation, including current controversies regarding the addition of a second bronchodilator versus initial treatment with two bronchodilators. Second, we discuss the step up from double bronchodilation to triple therapy while challenging current indications for inhaled steroid therapy and discussing triple therapy designs. Third, we discuss the step down from triple therapy to double bronchodilation while evaluating the effect of this downshift in risk categories on the patient according to the new classifications. Finally, we discuss the step down from double to single bronchodilation, with a special focus on safety. We believe this review will help to highlight the most relevant discussion points regarding the treatment of COPD in a manner that will stimulate and guide related clinical research.

Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration. METHODS: Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored. FINDINGS: Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy. CONCLUSIONS: Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation. FUNDING: This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation.

Exploring Current Concepts and Challenges in the Identification and Management of Early-Stage COPD.

The need to improve health outcomes, as well as disease prognosis, has led clinicians and researchers to propose new ways of identifying COPD in its earliest forms. This initiative is based on the hypothesis that an earlier intervention would have a greater prognostic impact. However, the operational definition of a patient in the initial stages of the disease is complex, and there is still no unanimously accepted definition. GOLD has recently proposed different concepts to identify COPD in its early stages, such as COPD in young people or COPD with mild functional impairment. In addition, GOLD proposes two other concepts, called pre-COPD (symptomatic non-obstructive patients) and PRISm (preserved ratio with impaired spirometry), which aim to identify the patient at risk of developing this chronic airflow obstruction. However, despite the attractiveness of these concepts, none have been taken up universally by the medical community. A universally accepted identification of how to define COPD in its early stages is necessary as a preliminary step in order to design clinical trials to find out the best way to treat these patients. This review deals with these concepts of COPD at the onset of the disease, highlighting their importance and the problems involved in identifying them as therapeutic targets in real clinical practice.

False negatives in the newborn screening for cystic fibrosis in Western Andalusia: Results from a 10-year experience.

Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, with an incidence of 1:5000 live births. In 2011, the screening of CF was implemented in the Andalusian Public Health newborn screening program by using immunoreactive trypsinogen and chloride sweat test (IRT/IRT/sweat test) determinations. Since then, 79 children have been diagnosed with CF in our health area (Western Andalusia). The aim of this study was to evaluate the efficiency of this screening method and to examinate the characteristics of those CF infants who had a negative screening but who were later diagnosed. In the 2011-2021 period 462,049 newborns were screened for CF using a two-step IRT determination and chloride sweat test. Sixty-three infants were diagnosed with CF in our health area thanks to the screening, and 15 CF children had a negative screening result and were finally diagnosed by molecular sequencing of the CFTR gene. The most frequent symptoms that led to the diagnosis of those false negative (FN) patients were hyponatremic dehydration (mean age 9.75 ± 1.5 months) and recurrent wheezing (mean age 24 ± 14.5 months). The molecular analysis of the CFTR gene on those FN showed a diversity of genotypes, identifying more than 10 different mutations. CONCLUSION: The rate of FN patients obtained in this study is inadmissibly high, and the protocol used in this region has not been updated despite the advances in genetic testing in the past 10 years. An improvement on CF newborn screening should be implemented, adding molecular analysis of the CFTR gene.

[Results of the Implementation of a Case-Finding Program for Alpha-1 Antitrypsin Deficiency in COPD Patients]. / Resultados de la implementación de un programa de detección de casos de déficit de alfa-1 antitripsina en pacientes con EPOC.

Objectives: Currently, the identification of new cases of alpha-1 antitrypsin deficiency (AATD) continues to be one of the great challenges facing the disease. The present study aims to perform an analysis of the results of the implementation of a systematic case detection program of AATD for patients with chronic obstructive pulmonary disease. Material and methods: Cross-sectional observational study in which the results of AAT screening until December 2022 were analyzed. The cases studied were divided into three periods: (1) no systematic case detection until 2013; (2) systematic case detection of S and Z alleles for cases with AAT < 90 mg/dL until 2018, and (3) systematic case detection of 14 mutations for cases with AAT < 120 mg/dL since 2018. Results: A total of 471 cases were studied, of which 306 (65.0%) were carriers of some mutation related to HAD. The number of detected cases of all mutations with their percentage against those studied in each period was respectively: 6 (100%), 48 (88.8%) and 253 (61.5%). If we limit to severe mutations (AAT < 57.2 mg/dL), the distribution by periods was respectively: 3 (50.0), 10 (18.5%) and 17 (4.1%). Conclusions: The present study describes the changes in the detection of patients carrying DAAT-related alleles with three different case identification policies. The data support the use of systematic case detection system in the COPD patient population.

Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease.

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. METHODOLOGY: Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. RESULTS: Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. CONCLUSIONS: ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug.

Deconstructing Phenotypes in COPD: an Analysis of the TRACE Cohort. / Deconstruyendo los fenotipos en la EPOC: un análisis de la cohorte TRACE.

OBJECTIVES: In a clinical phenotype-based management strategy for COPD, it would be preferable to at least assign all patients to a phenotype, but to a single phenotype only. The aim of this study was to evaluate whether all patients are assigned to one and only one phenotype using the Spanish COPD guidelines (GesEPOC) and to evaluate the criteria that define these categories. METHOD: The Time-based Register and Analysis of COPD Endpoints study (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients attending annual visits since 2012, which collects GesEPOC phenotypes. Although the GesEPOC recommends that patients considered to be at low risk are not phenotyped, an analysis of the criteria for identifying high- and low-risk phenotypes was performed, comparing the distribution of phenotypes and the criteria applied between these 2 groups. RESULTS: The cohort included 970 patients with a confirmed diagnosis of COPD, divided into 427 (44.02%) low-risk and 543 (55.9%) high-risk patients. The most frequent phenotype was the non-exacerbator (44.9% of high-risk patients). Overall, 20.6% of low-risk patients met criteria for asthma-COPD overlap syndrome, while 9.2% of the cohort did not meet the diagnostic criteria for any phenotype, and 19.1% met the criteria for 2 phenotypes, with no differences between risk groups. CONCLUSIONS: Our data highlight some of the weaknesses of the current clinical phenotype strategy, revealing overlapping categories in some cases, and patients to whom no phenotype was assigned.

Inflammatory response in human lung cells stimulated with plasma from COPD patients.

Background: Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response. Methods: We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis- COPD), and four smokers or ex-smokers without COPD as controls. Non-stimulated cells were used as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA. Results: Cells stimulated with plasma from COPD patients and non-COPD smoker subjects produced higher CRP, IL- 8 and MMP-9 levels, an increase for COPD in CRP (p=0.029) in epithelial cells and IL-8 (p=0.039) in fibroblasts and decrease for MMP-9 (p=0.039) in fibroblasts, compared with non-stimulated cells. The response was higher in epithelial cells for IL-8 (p=0.003) and in fibroblasts for MMP-9 (p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts. Conclusions: Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype.

Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine.

In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein's dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored.

Methodologies for the Determination of Blood Alpha1 Antitrypsin Levels: A Systematic Review.

BACKGROUND: The study of hematic concentrations of alpha1 antitrypsin (AAT) is currently one step in the diagnosis of AAT deficiency. To try to clarify the relevance of the laboratory techniques, we carried out a systematic review of the literature. METHODS: Studies evaluating the quantification of AAT in peripheral blood were searched in PubMed in July 2021. The selection criteria included (1) any type of study design that included a quantification of AAT in peripheral blood; (2) studies written in English or Spanish; (3) studies evaluating human beings; and (4) studies involving adults. RESULTS: Out of 207 studies, the most frequently used techniques were nephelometry (43.9%), followed by ELISA (19.8%) and turbidimetry (13.5%). Altogether, 182 (87.9%) cases expressed their results in units of gram, while 16 (7.7%) articles expressed them in units of mole. Only 2.9% articles referred to the standard used, 43.5% articles indicated the commercial kit used, and 36.2% indicated the analyzer used. CONCLUSIONS: The technical aspects of these determinations are not always reported in the literature. Journals should be attentive to these technical requirements and ensure that they are included in the works in which AAT is determined in order to ensure a correct interpretation of the study findings.

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.

Predictors of Single Bronchodilation Treatment Response for COPD: An Observational Study with the Trace Database Cohort.

Chronic obstructive pulmonary disease (COPD) patients constitute a heterogeneous population in terms of treatment response. Our objective was to identify possible predictive factors of response to treatment with single bronchodilation monotherapy in patients diagnosed with COPD. The Time-based Register and Analysis of COPD Endpoints (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients who have been attending annual visits since 2012. Patients who were kept on a single bronchodilator during the first year of follow-up were selected. The responders were defined according to all of the following variables: any improvement in morning post-dose forced expiratory volume in 1 s or deterioration <100 mL, no change or improvement in dyspnea score, and no occurrence of exacerbations. Significant and plausible variables were analyzed using a proportional hazard Cox regression for single bronchodilator responders. We analyzed 764 cases, of whom 128 (16.8%) were receiving monotherapy with one bronchodilator. Of these, 85 patients (66.4%) were responders. Factors affecting responder status were: female gender (hazard ratio (HR) 0.276; 95% confidence interval (CI) 0.089-0.858), dyslipidemia (HR 0.436; 95%CI 0.202-0.939), not performing regular exercise (HR 0.523; 95%CI 0.254-1.076), active smoking (HR 0.413; 95%CI 0.186-0.920), and treatment adherence (HR 2.527; 95%CI 1.271-5.027). The factors associated with a single bronchodilation response are mainly non-pharmacological interventions and comorbidities.

Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy.

Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. Subsequently, the publication of the results of the main clinical trials showing a decrease in the progression of pulmonary emphysema has led to a debate over a possible change in the main objective of treatment, from biochemical efficacy to clinical efficacy in terms of lung densitometry deterioration prevention. This new paradigm has produced a series controversies and unanswered questions which face clinicians managing AAT deficiency. In this review, the concepts that led to the approval of AAT replacement therapy are reviewed and discussed under a new prism of achieving clinical efficacy, with the reduction of lung deterioration as the main objective. Here, we propose the use of current knowledge and clinical experience to face existing challenges in different clinical scenarios, in order to help clinicians in decision-making, increase interest in the disease, and stimulate research in this field.

Integrating Comorbidities and Phenotype-Based Medicine in Patient-Centered Medicine in COPD.

Despite recent notable innovations in the management of chronic obstructive pulmonary disease (COPD), no major advances in patient-centered medicine have been achieved. Current guidelines base their proposals on the average results from clinical trials, leading to what could be termed 'means-based' medical practice. However, the therapeutic response is variable at the patient level. Additionally, the variability of the clinical presentation interacts with comorbidities to form a complex clinical scenario for clinicians to deal with. Consequently, no consensus has been reached over a practical approach for combining comorbidities and disease presentation markers in the therapeutic algorithm. In this context, from the patients' first visit, the clinician faces four major dilemmas: (1) establishing the correct diagnosis of COPD as opposed to other airway diseases, such as bronchial asthma; (2) deciding on the initial therapeutic approach based on the clinical characteristics of each case; (3) setting up a study strategy for non-responding patients; (4) pursuing a follow-up strategy with two well-defined periods according to whether close or long-term follow-up is required. Here, we will address these major dilemmas in the search for a patient-centered approach to COPD management and suggest how to combine them all in a single easy-to-use strategy.

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.

A Mobile Health Solution Complementing Psychopharmacology-Supported Smoking Cessation: Randomized Controlled Trial.

BACKGROUND: Smoking cessation is a persistent leading public health challenge. Mobile health (mHealth) solutions are emerging to improve smoking cessation treatments. Previous approaches have proposed supporting cessation with tailored motivational messages. Some managed to provide short-term improvements in smoking cessation. Yet, these approaches were either static in terms of personalization or human-based nonscalable solutions. Additionally, long-term effects were neither presented nor assessed in combination with existing psychopharmacological therapies. OBJECTIVE: This study aimed to analyze the long-term efficacy of a mobile app supporting psychopharmacological therapy for smoking cessation and complementarily assess the involved innovative technology. METHODS: A 12-month, randomized, open-label, parallel-group trial comparing smoking cessation rates was performed at Virgen del Rocío University Hospital in Seville (Spain). Smokers were randomly allocated to a control group (CG) receiving usual care (psychopharmacological treatment, n=120) or an intervention group (IG) receiving psychopharmacological treatment and using a mobile app providing artificial intelligence-generated and tailored smoking cessation support messages (n=120). The secondary objectives were to analyze health-related quality of life and monitor healthy lifestyle and physical exercise habits. Safety was assessed according to the presence of adverse events related to the pharmacological therapy. Per-protocol and intention-to-treat analyses were performed. Incomplete data and multinomial regression analyses were performed to assess the variables influencing participant cessation probability. The technical solution was assessed according to the precision of the tailored motivational smoking cessation messages and user engagement. Cessation and no cessation subgroups were compared using t tests. A voluntary satisfaction questionnaire was administered at the end of the intervention to all participants who completed the trial. RESULTS: In the IG, abstinence was 2.75 times higher (adjusted OR 3.45, P=.01) in the per-protocol analysis and 2.15 times higher (adjusted OR 3.13, P=.002) in the intention-to-treat analysis. Lost data analysis and multinomial logistic models showed different patterns in participants who dropped out. Regarding safety, 14 of 120 (11.7%) IG participants and 13 of 120 (10.8%) CG participants had 19 and 23 adverse events, respectively (P=.84). None of the clinical secondary objective measures showed relevant differences between the groups. The system was able to learn and tailor messages for improved effectiveness in supporting smoking cessation but was unable to reduce the time between a message being sent and opened. In either case, there was no relevant difference between the cessation and no cessation subgroups. However, a significant difference was found in system engagement at 6 months (P=.04) but not in all subsequent months. High system appreciation was reported at the end of the study. CONCLUSIONS: The proposed mHealth solution complementing psychopharmacological therapy showed greater efficacy for achieving 1-year tobacco abstinence as compared with psychopharmacological therapy alone. It provides a basis for artificial intelligence-based future approaches. TRIAL REGISTRATION: ClinicalTrials.gov NCT03553173; https://clinicaltrials.gov/ct2/show/NCT03553173. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/12464.

Status of and strategies for improving adherence to COPD treatment.

Despite the wide application of adherence as a concept, the definition, evaluation and improvement of the adherence to treatment by patients with chronic obstructive pulmonary disease (COPD) still present some challenges. First, it is necessary to clearly define the concepts of treatment adherence, compliance and persistence. Second, it is critical to consider the various methods of evaluating and quantifying adherence when interpreting adherence studies. In addition, the advantages and disadvantages of the different ways of measuring treatment adherence should be taken into account. Another subject of some debate is the number of variables associated with COPD treatment adherence. Adherence is a complex concept that goes beyond the dosage or the use of inhalation devices, and a number of variables are involved in determining adherence, from the clinical aspects of the disease to the patient's confidence in the doctor's expertise and the level of social support experienced by the patient. Notably, despite these challenges, the importance of adherence has been well established by clinical trials and routine clinical practice. The available evidence consistently shows the substantial impact that a lack of adherence has on the control of the disease and its long-term prognosis. For these reasons, the correct evaluation of therapeutic adherence should be a key objective in clinical interviews of patients. In recent years, various initiatives for improving adherence have been explored. All these initiatives have been based on patient education. Therefore, health care professionals should be aware of the issues pertaining to adherence and take the opportunity to educate patients each time they contact the health care system.