Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Clinical usefulness of serum angiotensin converting enzyme in silicosis.

INTRODUCTION: Silicosis is an irreversible and incurable disease. Preventive measures to eliminate exposure are the only effective way to reduce morbidity and mortality. In such situations, having a biomarker for early diagnosis or to predict evolution would be very useful in order to improve control of the disease. The elevation of serum angiotensin-converting enzyme (sACE) in silicosis has been described in previous studies, although its relationship with severity and prognosis is not clear. AIMS: To determine the levels of sACE in a cohort of patients with exposure to silica dust with and without silicosis, and to assess their impact on the prognosis of the aforementioned patients. METHOD: Prospective observational study on patients treated in a silicosis clinic from 2009 to 2018. sACE levels and pulmonary function tests were performed. Radiological progression was assessed in patients who had already had 2 X-rays of the thorax and / or two CT scans with at least a 1-year interval, from the time of inclusion in the study. RESULTS: A total of 413 cases of silicosis were confirmed, as well as 73 with exposure to silica dust but without silicosis. The mean sACE level for healthy subjects was 27.5±7.3U/L, for exposed patients without silicosis it was 49.6±24.2U/L, for simple silicosis it was 57.8±31,3U/L and for complicated silicosis it was 74.5±38.6U/L. Patients with a higher sACE generally progressed radiologically during follow-up (73.3±38.0 vs. 60.4±33.7; p<.001) and so the category of silicosis changed (73,9±38.1 vs. 62.5±34.6; p<.021). CONCLUSIONS: sACE was elevated in patients with silicosis, and the greater its severity, the higher it was, which is associated with disease progression measured radiologically or as a category change of silicosis.

Recurrence of primary spontaneous pneumothorax: Associated factors.

INTRODUCTION: Determining the risk of recurrence of primary spontaneous pneumothorax is challenging. The objective of this study was to develop a risk assessment model to predict the probability of recurrence in patients with spontaneous pneumothorax. METHODS: A retrospective study was performed of all episodes of pneumothorax diagnosed in the last 12 years in a hospital, in patients not initially submitted to surgery. Logistic regression was used to estimate the probability of recurrence. Based on a set of variables, a predictive model was built with its corresponding ROC curve to determine its discrimination power and diagnostic precision. RESULTS: Of the 253 patients included, 128 (50.6%) experienced recurrence (37% within the first year). Recurrence was detected within 110 days in 25% of patients. The median of time to recurrence for the whole population was 1120 days. The presence of blebs/bullae was found to be a risk factor of recurrence (OR: 5.34; 95% CI: 2.81-10.23; p=0.000), whereas chest drainage exerted protective effect (OR: 0.19; 95% CI: 0.08-0.40; p=0.000). The variables included in the regression model constructed were hemoglobin and leukocyte count in blood, treatment received, and presence of blebs/bullae, with a fair discriminative power to predict recurrence [AUC=0.778 (95% CI: 0.721-0.835)]. CONCLUSION: The overall recurrence rate was high and was associated with the presence of blebs/bullae, failure to perform an active intervention (chest drainage) and low levels of hemoglobin and leukocytes in blood. Recurrence rarely occurs later than three years after the first episode. Once validated, this precision model could be useful to guide therapeutic decisions.

Recent epidemiological trends in extrapulmonary TB in Galicia, Spain.

OBJECTIVE: To describe the epidemiological trends and characteristics of extrapulmonary tuberculosis (EPTB) in Galicia, Spain, from 2000 to 2019.METHODS: This was a retrospective cohort study based on data from the Galician TB information system.RESULTS: Of the total number of TB cases (n = 15,871), 5,428 (34.2%) had EPTB. The absolute number of cases and incidence of EPTB decreased dramatically (from 480 cases and 17.8 cases/100,000 in 2000, to 172 and 6.4 cases/100,000 in 2019, respectively), with a mean annual decrease of respectively 64% and 4.7% for absolute cases and incidence rates. The risk for EPTB was higher in men than in women (RR 3.86, 95% CI 3.66-4.07). The most frequent age group was 15-44 years (2,234 patients, 41.2%); overall reductions per age group were 82% (0-14 years), 75% (15-44 years), 44% (45-64 years) and 63% (≥65 years), with statistically significant differences. The most frequently locations were the pleura (1,916 cases; 35.3%) and the lymph nodes (1,504; 27.7%).CONCLUSION: The incidence of EPTB in Galicia has decreased significantly in the last 20 years. The epidemiological characteristics have not changed, except for the number of patients with risk factors. This improvement of EPTB epidemiological trends coincides with the implementation of the programme for the prevention and control of TB, which suggests that it has been very effective in the control of the EPTB.

Diesel exhausts particles: Their role in increasing the incidence of asthma. Reviewing the evidence of a causal link.

Exposure to air pollutants has been correlated with an increase in the severity of asthma and in the exacerbation of pre-existing asthma. However, whether or not environmental pollution can cause asthma remains a controversial issue. The present review analyzes the current scientific evidence of the possible causal link between diesel exhaust particles (DEP), the solid fraction of the complex mixture of diesel exhaust, and asthma. The mechanisms that influence the expression and development of asthma are complex. In children prolonged exposure to pollutants such as DEPs may increase asthma prevalence. In adults, this causal relation is less clear, probably because of the heterogeneity of the studies carried out. There is also evidence of physiological mechanisms by which DEPs can cause asthma. The most frequently described interactions between cellular responses and DEP are the induction of pulmonary oxidative stress and inflammation and the activation of receptors of the bronchial epithelium such as toll-like receptors or increases in Th2 and Th17 cytokines, which generally orchestrate the asthmatic response. Others support indirect mechanisms through epigenetic changes, pulmonary microbiome modifications, or the interaction of DEP with environmental antigens to enhance their activity. However, in spite of this evidence, more studies are needed to assess the harmful effects of pollution - not only in the short term in the form of increases in the rate of exacerbations, but in the medium and long term as well, as a possible trigger of the disease.

The CD14 (-159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes.

LPS-ligation to CD14/TLR-4 on monocytes/macrophages triggers the production of IL-12-family cytokines. IL12/18 promote TH1-differentiation, counteracting the TH2-driven asthma. Therefore, CD14 modulation could alter the TH2-differentiation and should be taken into account when studying asthma. To analyse the alteration in CD14 levels and its association with CD14 (-159 C/T) SNP (rs2569190) in Caucasian adults with stable allergic asthma, we performed a cross-sectional study (277 healthy subjects vs. 277 patients) where clinical parameters, CD14 values and the CD14 (-159 C/T) SNP were studied. Apart from typical biomarkers, we found an increment of neuron-specific enolase (NSE) in allergic asthma, probably linked to monocyte activity. Indeed, we evidenced increased monocyte numbers, but lower CD14 expression and normalised sCD14 values in patients. Moreover, we noticed an association of the T allele (P = 0.0162) and TT genotype (P = 0.0196) of the CD14 SNP with a decreased risk of allergic asthma and augmented sCD14 levels. In conclusion, monocyte CD14 expression and normalized sCD14 values were reduced in stable state asthmatics, and this could be related to the presence of an expanded CD14low monocyte subset. This study also demonstrates that the CD14 (-159 C/T) polymorphism is a risk factor for moderate-severe allergic asthma in adult Caucasians.

Expansion of a CD26low Effector TH Subset and Reduction in Circulating Levels of sCD26 in Stable Allergic Asthma in Adults.

BACKGROUND AND OBJETIVE: The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma. METHODS: Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants. RESULTS: In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P<.001). CD26 expression on lymphocytes was higher in asthmatics, while serum sCD26 was lower in women and patients. The latter finding could be associated with an expanded CD25low/CD26low/CD127low subset of effector CD4+ T cells in allergic asthma, with no changes in Treg percentages. However, women showed an increased Teff/Treg ratio, which could explain their greater susceptibility to asthma. CONCLUSIONS: Allergic asthma causes an increment in CD25lowCD26low helper T cells detected in stable stages. These changes are mirrored in serum and should be considered in the light of the downmodulating role of CD26 in major chemokines related to the pathogenesis of asthma such as CCL11 (eotaxin), CCL5 (RANTES), and CXCL12a (SDF-1α).

Asthma exacerbations: risk factors for hospital readmissions.

OBJECTIVE: The aim of our study is to analyse hospital readmissions due to asthma, as well as the factors associated with their increase. STUDY DESIGN: We carried out a retrospective study including all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. METHODS: The data were gathered by two members of the research team, by reviewing the clinical records. The first hospital admission of each patient was included for this study. An early readmission (ER) was defined as that which occurred in the following 15 days after hospital discharge and late readmission (LR) to that occurring from 16 days after discharge. RESULTS: This study included 2166 hospital admissions and 1316 patients, with a mean age of 62.6 years. Of the 1316 patients analysed, 36 (2.7%) had one ER and 313 (23.8%) one LR. The only factor independently associated with a higher probability of an ER was poor lung function. A higher probability of LR was associated with a greater severity of the asthma (OR: 17.8, for severe asthma versus intermittent asthma), to have had any hospital admission in the previous year (OR: 3.5) and the use of a combination of ICS-LABA as maintenance treatment. CONCLUSIONS: About 25% of the patients in our area admitted to hospital due to asthma exacerbation had repeat episodes of hospitalisation.

Cross-sectional study about impact of parental smoking on rhinitis symptoms in children.

OBJECTIVE: Assess the prevalence of rhinitis and exposure to environmental tobacco smoke (ETS) of children in our community and its relationship with symptoms of rhinitis METHODS (DESIGN, SETTING, PARTICIPANTS, MAIN OUTCOME MEASURES): Cross-sectional study using questionnaire on rhinitis of the International Study of Asthma and Allergies in Childhood, in children (6-7 years) and adolescents (13-14 years). Categories: "rhinitis ever", "recent rhinitis", "recent rhinoconjunctivitis", "severe rhinoconjunctivitis". Parental smoking: (i) neither parent smokes; (ii) only the mother smokes; (iii) only the father smokes; and (iv) both parents smoke. Odds ratio of the prevalence of symptoms of rhinitis according to ETS exposure was calculated using logistic regression. RESULTS: 10 690 children and 10 730 adolescents. The prevalence of "rhinitis ever" in children: 29.4%, "recent rhinitis" 24%, "recent rhinoconjunctivitis" 11.5% and "severe rhinoconjunctivitis" 0.1%. In adolescents: 46.2%, 34.5%, 16.2% and 0.2%, respectively. Environmental tobacco smoke exposure in the home occurred in 51% of cases. Parental smoking was associated with a higher prevalence of forms of rhinitis in adolescents when only the mother was a smoker. In children when both parents were smokers. CONCLUSION: Rhinitis is highly prevalent in our community. Environmental tobacco smoke exposure is still very common. The relationship between ETS and rhinitis symptoms in children of this community is not as robust as that found for asthma.

Behaviour of nucleated cells in various types of pleural effusion. / Comportamiento de las células nucleadas en los distintos tipos de derrame pleural.

INTRODUCTION: To know the behavior of cellular components of pleural fluid can help focus the differential diagnosis of a pleural effusion. Our objective was to assess their composition in different types of pleural effusions and assess whether it provides relevant clinical information. PATIENTS AND METHODS: Observational, cross-sectional and retrospective study in which the cellular components of pleural effusions of different etiology were analyzed. Pleural effusions were classified as neutrophilic, lymphocytic (≥50% of each one of them), eosinophilic (≥10%) or mesothelial (>5%) and were grouped into six diagnostic categories RESULTS: 1.467 patients were studied (354 heart failure; 59 other transudates; 349 paraneumonic; 133 tuberculous; 397 malignant and 175 other exudates). The predominance cell was lymphocytic in heart failure (44,4%), uncomplicated parapneumonic (29,2%), tuberculosis (88%) and malignant (49,6%); neutrophilic in parapneumonic (57%) and malignant (9,6%); eosinophilic in malignant (6,3%) and mesotelial in tuberculosis (12%). The most frequent etiologies with lymphocyte count ≥80% were tuberculosis (35,1%) and malignant (23,3%). Parameters with higher discriminating accuracy were: leukocytes (transudates: AUC 0,835) and percentage of neutrophils (empyemas: AUC 0,906 and complicated parapneumonic+empyemas: AUC 0,907). CONCLUSIONS: Nucleated cell counts will help focus the etiology of pleural effusions, since each etiology often have a characteristic cell predominance. The percentage of nucleated cells in pleural fluid not ruled out tuberculosis if there is a high count of mesothelial cells, nor a parapneumonic effusion with lymphocytic predominance, or malignancy with ≥80% lymphocytes.

Factors associated with the incidence of serious adverse events in patients admitted with COPD acute exacerbation.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of hospitalization. Patient outcome and prognosis following AECOPD are variable. The aim of this study is to identify the factors associated with the incidence of serious adverse events (SAE), defined as need for ICU admission, noninvasive ventilation, death during hospitalization or early readmission, in those patients admitted with AECOPD. METHODS: We conducted a retrospective study by reviewing the medical records of all patients admitted with AECOPD in the University Hospital Complex of Santiago de Compostela in 2007 and 2008. To identify variables independently associated with SAE incidence, we conducted a logistic regression including those variables which proved to be significant in the univariate analysis. RESULTS: 757 patients were assessed (mean age 74.8 years, SD 11.26), 77.2 % male, and 186 (24.6 %) of the patients assessed experienced an SAE. Factors associated with SAE in multivariate analysis were anticholinergic therapy (OR 3.19; CI 95 %: 1.16; 8.82), oxygen therapy at home (OR 3.72; CI 95 %: 1.62; 8.57), oxygen saturation at admission (OR 0.93; CI 95 %: 0.88; 0.99) and serum albumin (OR 0.26; CI 95 %: 0.1; 0.66). CONCLUSION: Oxygen therapy at home, anticholinergic therapy as baseline treatment, lower oxygen saturation at admission and lower serum albumin level seem to be associated with higher incidence of SAE in patients with AECOPD.

Symptoms, location and prognosis of pulmonary embolism.

BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is a common disease with variable symptoms and high overall mortality. The clinical relevance of the extent of PE is still debatable, and the role of anticoagulation in patients with subsegmental involvement has been contested. Our objective is to describe the clinical details of patients with PE in our hospital and to analyze their prognosis based on the extent of the disease. MATERIALS AND METHODS: Retrospective study of 313 patients diagnosed with PE by chest computed tomography (CT) scan at the Hospital Complex of Pontevedra in Spain for six years. Predictors of mortality were determined by multivariate analysis. RESULTS: Women accounted for 56% of patients, and patient median age was 70 years (interquartile range 53-78 years). Subsegmental PE accounted for 7% of all cases; these patients were younger and had lower comorbidity; they reported chest pain more often, performed better in blood gas analysis and none of them had proximal deep vein thrombosis (DVT). Patients with subsegmental PE had a higher survival rate. Factors independently associated with mortality were cancer diagnosis and higher comorbidity. CONCLUSIONS: Patients with subsegmental PE clinically differ from those with more proximal PE. Underlying diseases have more influence on the prognosis than the extent of the disease.

Timeliness of care and prognosis in patients with lung cancer.

BACKGROUND: Timeliness of care is an important dimension of health care quality. The determining factors of less timely care and their influence on the survival of patients with lung cancer (LC) remain uncertain. AIMS: To analyse the delays in the diagnosis and treatment of LC in our health area, the factors associated with the timeliness of care and their possible relationship with the survival of these patients. METHODS: A retrospective study was conducted on all patients with a cytohistologically confirmed diagnosis of LC between 1 June 2005 and 31 May 2008. The time delays for consultation (specialist delay), diagnosis (diagnosis delay), and treatment (treatment delay), were analysed, as well as the factors associated with these delays and the influence of the timeliness of care on survival. RESULTS: A total of 307 cases were included (87 % males). The mean specialist delay was 53.6 days (median 35 days), diagnosis delay 31.5 days (median 18 days), treatment delay 23.5 days (median 14 days). The greater age of the patient and a more advanced stage were associated with a shorter specialist delay. Male sex, a more advanced stage, and poor general status were associated with a shorter treatment delay. The survival is longer in patients with a longer treatment delay. CONCLUSIONS: The delay in the diagnosis in our population seems to be excessively long. The greater the age, a more advanced tumour stage, male sex, and poor general health status are associated with shorter delays. A longer treatment delay is associated with a longer survival.