Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2 / Relationship between obstructive sleep apnea and type 2 diabetes mellitus

Introducción: La asociación entre la apnea obstructiva del sueño (AOS) y el metabolismo de la glucosa sigue siendo controvertida. Este estudio investiga la relación entre la AOS y la diabetes mellitus tipo 2 (DM) y prediabetes (preDM) incidentes, así como el efecto del tratamiento con presión positiva continua en la vía aérea (CPAP) a largo plazo. Métodos: Estudio de seguimiento en cohorte retrospectiva clínica de pacientes con AOS y controles seleccionados de manera aleatoria. Los datos sobre DM incidente y preDM, así como de la CPAP se obtuvieron de los registros hospitalarios. La relación entre AOS basal y la DM incidente se examinó con modelos de regresión de Cox. Resultados: De un total de 356 pacientes, 169 con AOS y 187 controles fueron seguidos por una mediana de 98 meses; 47 enfermos (13,2%) desarrollaron DM y 43 (12,1%) preDM. La incidencia acumulada a los cinco años de DM fue de 10,7% (6,5-13,9%). De los sujetos con preDM en la muestra basal, 87% evolucionaron a DM incidente. Se demuestra que el índice de masa corporal (IMC), la hipoxia nocturna y el índice de apnea hipopnea (IAH) son factores de riesgo para el desarrollo de DM, y que la CPAP los disminuye. Conclusiones: Los pacientes con AOS tienen mayor probabilidad de desarrollar DM. Los factores de riesgo implicados son el IMC, la hipoxia nocturna y el IAH. El uso regular de CPAP a largo plazo se asoció con una disminución de estos. (AU)

Introduction: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. Methods: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. Results: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5–13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. Conclusions: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk. (AU)

Effect of an intensive tobacco cessation program on the smoker narrative: A content analysis and grounded theory.

INTRODUCTION: The smoker's narrative during smoking quitting provides insight into aspects not fully explored in daily clinical practice. The aim of the study was to analyze the smoker narrative using two types of methodologies: content analysis and grounded theory, before and after smoking cessation intervention, provided to the smoker in a specialized Smoking Cessation Unit accredited by the Spanish Society of Pneumology and Thoracic Surgery. METHODS: A prospective observational study of current smokers included in a tobacco cessation program between 2017 and 2020 was conducted at the Smoking Cessation Unit of Santiago de Compostela Health Area, Spain. Routine clinical variables and patient narrative data were collected. A descriptive analysis of the sample, the content of the textual corpus, and a grounded theory were performed in semi-structured interviews at baseline and at follow-up at 6 months. RESULTS: A total of 116 patients were included (mean age 55.6 ± 10.6 years; 56.9% male; mean nicotine dependence score 5.7 ± 1.6). Quantitative analysis of the narrative shows that the most frequent phrases and words are associated with smoking, nicotine craving, and predisposition for smoking cessation. After the intervention, phrases related to the manifestation of abstinence, response to pharmacological treatment, and self-perception of smoking cessation were predominant. In the qualitative analysis, the most frequent categories in the smoker's textual corpus were dependence, motivation, and emotionality, which decreased after the intervention (11.4%, 21.4%, and 9.9%, respectively) accompanied by increased satisfaction (19.2%) and the manifestation of abstinence (21.5%). CONCLUSIONS: Motivation, nicotine dependence, and sensitivity to emotions are all closely intertwined in the current smoker narrative and can be modified as a consequence of treatment.

Relationship between obstructive sleep apnea and type 2 diabetes mellitus. / Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2.

INTRODUCTION: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. METHODS: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. RESULTS: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5-13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. CONCLUSIONS: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk.

Diabetes y apnea obstructiva del sueño. Un estudio de casos y controles / Diabetes and obstructive sleep apnoea: A case-control study

Introducción La apnea obstructiva del sueño (AOS) y la diabetes mellitus (DM) son enfermedades muy prevalentes frecuentemente asociadas. Su coexistencia se asocia de forma independiente con un aumento de la prevalencia de comorbilidades cardiovasculares. Al existir un infradiagnóstico de esta asociación, es necesario optimizar la sospecha clínica mediante el estudio de predictores independientes de DM o de prediabetes (preDM) en pacientes con AOS. Método Estudio de casos y controles, seleccionados de manera aleatoria simple y emparejados por sexo, índice de masa corporal (IMC) y edad, que pretende estudiar la asociación de la AOS con la DM y la preDM e identificar factores predictores independientes para ambas enfermedades, en las personas con AOS. Resultados Incluimos 208 casos con AOS y 208 controles, sin AOS. En los primeros, el 18,8% tenían DM, por solo el 10,1% en los segundos (p=0,00). La prevalencia de preDM fue del 41,8% vs el 10,6%, respectivamente (p=0,00). Ciento veinticuatro casos (59,6%) refirieron excesiva somnolencia diurna (ESD) (escala Epworth, 10,5±3,1) vs el 24,5% del grupo control (escala Epworth, 6,6±2,9). El índice de apnea-hipopnea (IAH) y los índices de desaturación de O2 (IDO, CT90 y CT80) fueron significativamente mayores en el grupo de casos. El riesgo de presentar DM se relacionó con la edad, la hipoxemia nocturna y la ESD. El riesgo de presentar preDM, con el IMC y con el IAH. Conclusiones La AOS se asocia a la DM y a la preDM. La edad, la hipoxemia nocturna y la ESD son predictores de DM. El IMC y el IAH lo son de la preDM. (AU)

Introduction Obstructive sleep apnoea (OSA) and diabetes mellitus (DM) are very prevalent diseases frequently associated. Their coexistence is independently associated with an increased prevalence of cardiovascular comorbidities. As this association is underdiagnosed, it is necessary to optimise clinical suspicion by studying independent predictors of DM or prediabetes (preDM) in patients with OSA. Method A simple randomised case-control study, matched for sex, body mass index (BMI) and age, aimed to study the association of OSA with DM and preDM and to identify independent predictors for both diseases in people with OSA. Results We included 208 cases with OSA and 208 controls without OSA. In the former, 18.8% had DM compared to only 10.1% in the latter (P=.00). Prevalence of preDM was 41.8% vs. 10.6%, respectively (P=.00). One hundred and twenty-four cases (59.6%) reported excessive daytime sleepiness (EDS) (Epworth scale, 10.5±3.1) vs. 24.5% of the control group (Epworth scale, 6.6±2.9). Apnoea-hypopnoea index (AHI) and O2 desaturation indices (IDO, CT90 and CT80) were significantly higher in the case group. The risk of MD was related to age, nocturnal hypoxaemia and EDS. The risk of pre-MD was related to BMI and AHI. Conclusions OSA is associated with DM and preDM. Age, nocturnal hypoxaemia and EDS are predictors of DM. BMI and AHI are predictors of pre-MD. (AU)

Diabetes y apnea obstructiva del sueño. Un estudio de casos y controles / Diabetes and obstructive sleep apnoea: A case-control study

Introducción La apnea obstructiva del sueño (AOS) y la diabetes mellitus (DM) son enfermedades muy prevalentes frecuentemente asociadas. Su coexistencia se asocia de forma independiente con un aumento de la prevalencia de comorbilidades cardiovasculares. Al existir un infradiagnóstico de esta asociación, es necesario optimizar la sospecha clínica mediante el estudio de predictores independientes de DM o de prediabetes (preDM) en pacientes con AOS. Método Estudio de casos y controles, seleccionados de manera aleatoria simple y emparejados por sexo, índice de masa corporal (IMC) y edad, que pretende estudiar la asociación de la AOS con la DM y la preDM e identificar factores predictores independientes para ambas enfermedades, en las personas con AOS. Resultados Incluimos 208 casos con AOS y 208 controles, sin AOS. En los primeros, el 18,8% tenían DM, por solo el 10,1% en los segundos (p=0,00). La prevalencia de preDM fue del 41,8% vs el 10,6%, respectivamente (p=0,00). Ciento veinticuatro casos (59,6%) refirieron excesiva somnolencia diurna (ESD) (escala Epworth, 10,5±3,1) vs el 24,5% del grupo control (escala Epworth, 6,6±2,9). El índice de apnea-hipopnea (IAH) y los índices de desaturación de O2 (IDO, CT90 y CT80) fueron significativamente mayores en el grupo de casos. El riesgo de presentar DM se relacionó con la edad, la hipoxemia nocturna y la ESD. El riesgo de presentar preDM, con el IMC y con el IAH. Conclusiones La AOS se asocia a la DM y a la preDM. La edad, la hipoxemia nocturna y la ESD son predictores de DM. El IMC y el IAH lo son de la preDM. (AU)

Introduction Obstructive sleep apnoea (OSA) and diabetes mellitus (DM) are very prevalent diseases frequently associated. Their coexistence is independently associated with an increased prevalence of cardiovascular comorbidities. As this association is underdiagnosed, it is necessary to optimise clinical suspicion by studying independent predictors of DM or prediabetes (preDM) in patients with OSA. Method A simple randomised case-control study, matched for sex, body mass index (BMI) and age, aimed to study the association of OSA with DM and preDM and to identify independent predictors for both diseases in people with OSA. Results We included 208 cases with OSA and 208 controls without OSA. In the former, 18.8% had DM compared to only 10.1% in the latter (P=.00). Prevalence of preDM was 41.8% vs. 10.6%, respectively (P=.00). One hundred and twenty-four cases (59.6%) reported excessive daytime sleepiness (EDS) (Epworth scale, 10.5±3.1) vs. 24.5% of the control group (Epworth scale, 6.6±2.9). Apnoea-hypopnoea index (AHI) and O2 desaturation indices (IDO, CT90 and CT80) were significantly higher in the case group. The risk of MD was related to age, nocturnal hypoxaemia and EDS. The risk of pre-MD was related to BMI and AHI. Conclusions OSA is associated with DM and preDM. Age, nocturnal hypoxaemia and EDS are predictors of DM. BMI and AHI are predictors of pre-MD. (AU)

Analysis of the quality of e-Consultations in chronic obstructive pulmonary disease.

INTRODUCTION: The quality of e-Consultations in the COPD is unknown. The objectives of this study were (i) to evaluate the quality of referrals; (ii) to define the characteristics of patients referred from Primary Care (PC) to the Unit of Pulmonology; and (iii) to describe differences between accepted and rejected patients. METHODS: A retrospective, observational study of e-Consultations requested by PC for suspected COPD throughout 2022. To quantify the quality of the e-Consultations, an arbitrary scale of 12 variables (score 0-10) was created. RESULTS: In total, 384 e-Consultations were reviewed, of which 167 (43.5 %) resulted in a face-to-face visit, and 217 (56.5 %) were rejected. No differences were observed between the two types of patients, except for confirmations of diagnostic suspicion of COPD [significantly higher in accepted patients (p = 0.042)]; physical examination data of rejected patients (more data provided; p = 0.015); and lung function (significantly better in rejected patients). The mean quality of referrals was acceptable (5.6 ± 2.1 score): 121 (31.3 %) had insufficient quality; 118 (30.5 %) acceptable; 75 (19.4 %) good, and 30 (7.8 %) excellent. Quality was low in half of the variables analyzed (6/12); acceptable in 3, and good in another 3. The capacity of resolution of referrals was good (one e-Consultation) in 199 requests (66.1 %); deficient (two e-Consultations) in 72 (23.9 %), and poor (≥3 e-Consultations) in 30 (10 %). Overdiagnosis was 40.2 % (86/214 e-Consultations). The risk could be classified in 247 patients (64.3 %; 135 low-risk; 90 high-risk). CONCLUSIONS: When adequate information is provided, e-Consultations help identify different levels of severity. However, the quality and capacity of resolution of referrals were suboptimal, with a high percentage of overdiagnoses.

Usefulness of a predictive model to hospitalize patients with low-risk community-acquired pneumonia.

INTRODUCTION: A high proportion of patients with low-risk community-acquired pneumonia (CAP) (classes I-III of the Pneumonia Severity Index) are hospitalized. The purpose of this study was to determine whether validated severity scales are used in clinical practice to make admission decisions, identify the variables that influence this decision, and evaluate the potential predictive value of these variables. MATERIALS AND METHODS: A prospective, observational study of patients ≥ 18 years of age with a diagnosis of low-risk CAP hospitalized or referred from the Emergency Department to outpatient consultations. A multivariate logistic regression predictive model was built to predict the decision to hospitalize a patient. RESULTS: The study population was composed of 1,208 patients (806 inpatients and 402 outpatients). The severity of CAP was estimated in 250 patients (20.7%). The factors that determined hospitalization were "abnormal findings in complementary studies" (643/806: 79.8%; due to respiratory failure in 443 patients) and "signs of clinical deterioration" [64/806 (7.9%): hypotension (16/64, 25%); hemoptoic expectoration (12/64, 18.8%); tachypnea (10/64, 15.6%)]. In total, ambulatory management was not contraindicated in 24.7% of hospitalized patients (199). The predictive model built to decide about hospitalization had a good power of discrimination (AUC 0.876; 95%CI: 0.855-0.897). CONCLUSIONS: Scales are rarely used to estimate the severity of CAP at the emergency department. The decision to hospitalize or not a patient largely depends on the clinical experience of the physician. Our predictive model showed a good power to discriminate the patients who required hospitalization. Further studies are warranted to validate these results.

[Diabetes and obstructive sleep apnoea: A case-control study]. / Diabetes y apnea obstructiva del sueño. Un estudio de casos y controles.

INTRODUCTION: Obstructive sleep apnoea (OSA) and diabetes mellitus (DM) are very prevalent diseases frequently associated. Their coexistence is independently associated with an increased prevalence of cardiovascular comorbidities. As this association is underdiagnosed, it is necessary to optimise clinical suspicion by studying independent predictors of DM or prediabetes (preDM) in patients with OSA. METHOD: A simple randomised case-control study, matched for sex, body mass index (BMI) and age, aimed to study the association of OSA with DM and preDM and to identify independent predictors for both diseases in people with OSA. RESULTS: We included 208 cases with OSA and 208 controls without OSA. In the former, 18.8% had DM compared to only 10.1% in the latter (P=.00). Prevalence of preDM was 41.8% vs. 10.6%, respectively (P=.00). One hundred and twenty-four cases (59.6%) reported excessive daytime sleepiness (EDS) (Epworth scale, 10.5±3.1) vs. 24.5% of the control group (Epworth scale, 6.6±2.9). Apnoea-hypopnoea index (AHI) and O2 desaturation indices (IDO, CT90 and CT80) were significantly higher in the case group. The risk of MD was related to age, nocturnal hypoxaemia and EDS. The risk of pre-MD was related to BMI and AHI. CONCLUSIONS: OSA is associated with DM and preDM. Age, nocturnal hypoxaemia and EDS are predictors of DM. BMI and AHI are predictors of pre-MD.

A pulmonary rehabilitation program reduces hospitalizations in chronic obstructive pulmonary disease patients: A cost-effectiveness study.

BACKGROUND: Although pulmonary rehabilitation (PR) is recommended in patients with chronic obstructive pulmonary disease (COPD), there is a scarcity of data demonstrating the cost-effectiveness and effectiveness of PR in reducing exacerbations. METHODS: A quasi-experimental study in 200 patients with COPD was conducted to determine the number of exacerbations 1 year before and after their participation in a PR program. Quality of life was measured using the COPD assessment test and EuroQol-5D. The costs of the program and exacerbations were assessed the year before and after participation in the PR program. The incremental cost-effectiveness ratio (ICER) was estimated in terms of quality-adjusted life years (QALYs). RESULTS: The number of admissions, length of hospital stay, and admissions to the emergency department decreased after participation in the PR program by 48.2%, 46.6%, and 42.5%, respectively (P < 0.001 for all). Results on quality of life tests improved significantly (P < 0.001 for the two tests). The cost of PR per patient and the cost of pre-PR and post-PR exacerbations were €1867.7 and €7895.2 and €4201.9, respectively. The PR resulted in a cost saving of €1826 (total, €365,200) per patient/year, and the gain in QALYs was+0.107. ICER was -€17,056. The total cost was <€20,000/QALY in 78% of patients. CONCLUSIONS: PR contributes to reducing the number of exacerbations in patients with COPD, thereby slowing clinical deterioration. In addition, it is cost-effective in terms of QALYs.

Development of prognostic models to estimate the probability of lung injury one year after COVID-19-related hospitalization-a prospective study.

Background: Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection still under study. The objectives of this study were to identify persistent pulmonary lesions 1 year after coronavirus disease 2019 (COVID-19) hospitalization and assess whether it is possible to estimate the probability that a patient develops these complications in the future. Methods: A prospective study of ≥18 years old patients hospitalized for SARS-COV-2 infection who develop persistent respiratory symptoms, lung function abnormalities or have radiological findings 6-8 weeks after hospital discharge. Logistic regression models were used to identify prognostic factors associated with a higher risk of developing respiratory problems. Models performance was assessed in terms of calibration and discrimination. Results: A total of 233 patients [median age 66 years [interquartile range (IQR): 56, 74]; 138 (59.2%) male] were categorized into two groups based on whether they stayed in the critical care unit (79 cases) or not (154). At the end of follow-up, 179 patients (76.8%) developed persistent respiratory symptoms, and 22 patients (9.4%) showed radiological fibrotic lesions with pulmonary function abnormalities (post-COVID-19 fibrotic pulmonary lesions). Our prognostic models created to predict persistent respiratory symptoms [post-COVID-19 functional status at initial visit (the higher the score, the higher the risk), and history of bronchial asthma] and post-COVID-19 fibrotic pulmonary lesions [female; FVC% (the higher the FVC%, the lower the probability); and critical care unit stay] one year after infection showed good (AUC 0.857; 95% CI: 0.799-0.915) and excellent performance (AUC 0.901; 95% CI: 0.837-0.964), respectively. Conclusions: Constructed models show good performance in identifying patients at risk of developing lung injury one year after COVID-19-related hospitalization.

Characteristics of pleural effusion due to amyloidosis.

The characteristics of patients with pleural amyloidosis (PA) are poorly known. A systematic review was performed of studies reporting clinical findings, pleural fluid (PF) characteristics, and the most effective treatment of PA. Case descriptions and retrospective studies were included. The review included 95 studies with a total sample of 196 patients. The mean age was 63 years, male/female ratio was 1.6:1, and 91.9% of patients were >50 years. The most common symptom was dyspnea (88 patients). PF was generally serious (63%), predominantly lymphocytic, and with the biochemical characteristics of transudates (43.4%) or exudates (42.6%). Pleural effusion was generally bilateral (55%) and <1/3 of the hemithorax (50%), although in 21% pleural effusion (PE) exceeded 2/3. Pleural biopsy was performed in 67 patients (yield: 83.6%; 56/67) and was positive in 54% of exudates and 62.5% of unilateral effusions. Of the 251 treatments prescribed, only 31 were effective (12.4%). The combination of chemotherapy and corticosteroids was effective in 29.6% of cases, whereas talc pleurodesis was effective in 21.4% and indwelling pleural catheter in 75% of patients (only four patients). PA is more frequent in adults from 50 years of age. PF is usually bilateral, serous, and indistinctly a transudate or exudate. A pleural biopsy can aid in diagnosis if effusion is unilateral or an exudate. Treatments are rarely effective and there may be definitive therapeutic options for PE in these patients.

Cost-Effectiveness of a New Outpatient Pulmonology Care Model Based on Physician-to-Physician Electronic Consultation.

Introduction: This study assesses the impact of an electronic physician-to-physician consultation program on the waiting list and the costs of a Pulmonology Unit. Materials and Methods: A prepost intervention study was conducted after a new ambulatory pulmonary care protocol was implemented and the capacity of the unit was adopted. In the new model, physicians at all levels of healthcare send electronic consultations to specialists. Results: In the preintervention year (2019), the Unit of Pulmonology attended 7,055 consultations (466 e-consultations and 6,589 first face-to-face visits), which decreased to 6,157 (3,934 e-consultations and 2,223 first face-to-face visits; 12.7% reduction) in the postintervention year (all were e-consultations). The mean wait time for the first appointment was 25.7 days in 2019 versus 3.2 days in 2021 (p < 0.001). In total, 43.5% of cases were solved via physician-to-physiciane-consultation. A total of 2,223 patients needed a face-to-face visit, with a mean wait time of 7.5 days. The mean of patients in the waiting listing decreased from 450.8 in 2019 to 44.8 in 2021 (90% reduction). The annual time devoted to e-consultations and first face-to-face visits following an e-consultation diminished significantly after the intervention (1,724 hours versus 2,312.8; 25.4% reduction). Each query solved via e-consultation represented a saving of €652.8, resulting in a total annual saving of €827,062. Conclusions: Physician-to-physiciane-consultations reduce waiting times, improve access of complex patients to specialty care, and ensure that cases are managed at the appropriate level. E-consultation reduces costs, which benefits both, society and the healthcare system.

Sarcoidosis. Disease progression based on radiological and functional course: Predictive factors.

BACKGROUND: Sarcoidosis is a multiorgan granulomatous disease with a variable course. OOBJECTIVES: The purpose of this study is to identify the patients that are more likely to experience disease progression. METHODS: A retrospective study in patients ≥18 years. Pulmonary function and radiological stage (Scadding criteria) were assessed at diagnosis, and at 1, 3 and 5 years. Sarcoidosis progression was established based on deterioration of radiological or pulmonary function (decrease ≥10% of FVC and/or ≥15% of diffusing capacity of the lung (DLCO). RESULTS: The sample included 277 caucasian patients [mean age, 50±13.6; 69.7% between 31-60 years; 56.3% men]. In total, 65% had stage II sarcoidosis, whereas only 8.3% had stage III/IV disease. Mean pulmonary function (FVC, FEV1, FEV1/FVC and DLCO) at diagnosis was 103±21.8, 96±22.2, 76.2±8 and 81.7±21.7, respectively. The percentage of patients with normal FVC and DLCO was 72.2% and 51.8%, respectively. Radiological stage did not change significantly during follow-up (5 years; p=0.080) and only progressed in 13 patients (5.7%). At 3 years, FVC improved, whereas DLCO exacerbated significantly (p<0.001 for the two). Disease progressed in 34.5% of the patients (57/165) whose pulmonary function and radiological stage were available (both baseline and at 3 years). Age was associated with disease progression [OR=1.04 (95%CI=1.01, 1.06)]. Risk increased by 4% for each year older a patient was at diagnosis. CONCLUSIONS: At 3 years, a third of patients experienced sarcoidosis progression. Age was the only factor associated with disease prognosis.

Characterisation of the blood RNA host response underpinning severity in COVID-19 patients.

Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.

Pulmonary Manifestations of Primary Humoral Deficiencies.

Primary immunodeficiencies are a group of conditions characterized by developmental or functional alterations in the immune system caused by hereditary genetic defects. Primary immunodeficiencies may affect either the innate or the adaptive (humoral and cellular) immune system. Pulmonary complications in primary humoral deficiencies are frequent and varied and are associated with high morbidity and mortality rates. The types of complications include bronchiectasis secondary to recurrent respiratory infections and interstitial pulmonary involvement, which can be associated with autoimmune cytopenias, lymphoproliferation, and a range of immunological manifestations. Early detection is key to timely management. Immunoglobulin replacement therapy reduces the severity of disease, the frequency of exacerbations, and hospital admissions in some primary humoral deficiencies. Therefore, the presence of pulmonary disease with concomitant infectious and/or autoimmune complications should raise suspicion of primary humoral deficiencies and warrants a request for immunoglobulin determination in blood. Once diagnosis is confirmed; early immunoglobulin replacement therapy will improve the course of the disease. Further studies are needed to better understand the pathogenesis of pulmonary disease related to primary humoral deficiencies and favor the development of targeted therapies that improve the prognosis of patients.

A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity.

Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.

[Effectiveness of smoking cessation programs of roll-your-own tobacco smokers in Galicia.] / Efectividad de los programas de cesación tabáquica en fumadores de tabaco de liar en Galicia.

OBJECTIVE: Currently in developed countries there is an increase in the consumption of roll your own tobacco, which is associated with a higher proportion of users of this form of tobacco who wish to make an attempt to quit. The objective of this study was to analyze the effectiveness of tobacco cessation interventions based on the type of tobacco consumed. METHODS: Longitudinal study of a cohort of 641 smokers recruited between 2015 and 2018 in a health area of Galicia included in smoking cessation programs, based on psychological counseling and pharmacological treatment. The characteristics and success of the intervention were evaluated in two groups: roll your own tobacco smokers (RYO) and manufactured tobacco smokers (MT). A logistic regression was performed to determine the probability of success in smoking cessation. The risk measure was the odds ratio (OR) with its 95% confidence interval. RESULTS: RYO users started at a younger age and had a lower sociocultural stratum than MT users. Interventions to quit smoking in RYO users were associated with less abstinence at 4 weeks (52% MT vs 38% LT) (OR: 0.5; 95% CI 0.35-0.99; p=0.045;) and at 3 months (42% TM vs 30% TL) (OR:0.6; 95% CI 0.33-0.98; p=0.04). CONCLUSIONS: Smoking cessation programs are less effective in short-term RYO users. There are no differences in long-term abstinence between the two groups.

OBJETIVO: Actualmente en los países desarrollados existe un aumento del consumo de tabaco de liar lo que se asocia a una mayor proporción de usuarios de esta forma de tabaco que desean realizar un intento de abandono. El objetivo de este estudio fue analizar la efectividad de las intervenciones de cesación tabáquica en función del tipo de tabaco consumido. METODOS: Estudio longitudinal de una cohorte de 641 fumadores reclutados entre 2015 y 2018 en un área sanitaria de Galicia incluidos en programas de deshabituación tabáquica, basados en el asesoramiento psicológico y en el tratamiento farmacológico. Se evaluaron las características y el éxito de la intervención en dos grupos: fumadores de tabaco de liar (TL) y fumadores de tabaco manufacturado (TM). Se realizó una regresión logística para determinar la probabilidad de éxito en la cesación tabáquica. La medida de riesgo fue el odds ratio (OR) con su intervalo de confianza al 95%. RESULTADOS: Los consumidores de TL se iniciaron a una edad más temprana y tenían un estrato sociocultural más bajo que los consumidores de TM. Las intervenciones para abandonar el tabaco en los consumidores de TL se asociaron a una menor abstinencia a las 4 semanas (52%TM vs 38% TL) (OR: 0,5; 95%IC 0,35-0,99; p=0,045;) y a los 3 meses (42%TM vs 30%TL) (OR:0,6; 95%IC 0,33-0,98; p=0,04). CONCLUSIONES: Los programas de cesación tabáquica son menos efectivas en los consumidores de TL a corto plazo. No se observan diferencias en la abstinencia a largo plazo entre ambos grupos.