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.

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.

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).

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.

Obesity and asthma: an association modified by age.

BACKGROUND: Some studies indicate some causal relationship between obesity and asthma, while others show inconsistent results. Our objective was to evaluate the prevalence of asthma according to obesity in children. METHODS: A cross-sectional study, following the ISAAC study methodology, was conducted on two randomly selected groups consisting of 6-7 year-old children (n=7485) and 13-14 year-old adolescents (n=8496). The asthma symptoms and potential risk factors were determined from the questionnaire. Overweight and obesity were defined based on the body mass index. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) and 95% confidence intervals. RESULTS: Obesity was associated with an increase in wheezing ever (OR: 1.35) and exercise-induced asthma (OR: 1.62) in the 6-7 year-old group. No significant relationship was observed in the adolescent population. CONCLUSION: Obesity was associated with a higher prevalence of asthma in young children, but not in adolescents.

Truck traffic related air pollution associated with asthma symptoms in young boys: a cross-sectional study.

OBJECTIVES: The aim of this study was to evaluate the influence of intensity of truck traffic on asthma symptomatology, and its relationship with age and gender. STUDY DESIGN: A cross-sectional study was conducted on children and adolescents from Galicia (North-West Spain). METHODS: Following the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC): children from schools randomly selected, answered a self-administered questionnaire included questions on asthma symptoms and some risk factors. The association between self-reported truck traffic on the street of residence and symptoms of asthma were investigated by logistic regression adjusted for body mass index, maternal education and parental smoking. RESULTS: Almost 40% of children in Galicia are exposed to the frequent and constant passing of heavy goods vehicles. The odds of 6-7 year-old boys having severe or exercise induced asthma is tripled when they live in streets with the constant passing of heavy goods vehicles, compared with those living in streets where these vehicles never pass. In adolescents and 6-7 year-old girls, no relationship was observed between truck traffic and asthma symptoms. CONCLUSIONS: The results of this study appear to support a distinct effect of truck traffic on asthma symptoms depending on the age and sex of the exposed population, being more harmful for young males.

Trends of asthma mortality in Galicia from 1993 to 2007.

INTRODUCTION: In the past few years, deaths due to asthma appear to decrease at least in Western countries; but there are significant variations between populations. The aim of this study is to describe the trends in deaths due to asthma between 1993 and 2007 in our community and to analyze any factors associated with this. METHODS: All cases, which had asthma as a cause of death, were included in the study. The mortality data were obtained from the official death certificate from the Deaths Register. Mortality relative risk, based on the calendar year, sociodemographic variables (age and gender), seasons, and days of the week, were estimated using a Poisson generalized linear model with a log-link. RESULTS: In the 15 years of the study period, a total of 1180 people had died due to asthma, mainly in winter (34.5%), women (64.5%), and advanced age (65 years or above; 84.6%). A tendency of decreased mortality in all age groups was observed during the period of the study, which was significant in both the sexes in the 35- to 64-year-old age group, and in males above 65 years. CONCLUSION: Death due to asthma is changing favorably in our community, with a tendency to decrease in the past few years. Advanced age, being female, and the winter period are associated with a higher mortality rate due to asthma.

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.

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.

[Lung involvement in pyoderma gangrenosum: a case report and review of the literature]. / Pioderma gangrenoso con afectación pulmonar: caso clínico y revisión de la literatura.

Pyoderma gangrenosum is a neutrophilic dermatosis that, in addition to its characteristic skin manifestations, can cause visceral alterations. Our patient was a 34-year-old woman with pyoderma gangrenosum that was exacerbated by iodine and that also affected the lungs. Other published cases of lung involvement in pyoderma gangrenosum are reviewed and we discuss the possible exacerbation of this disease by iodine. Lung involvement is the most common extracutaneous manifestation of pyoderma gangrenosum and the main differential diagnosis is then with Wegener granulomatosis. It is important to remember the possible presentation of extracutaneous manifestations of pyoderma gangrenosum, including particularly lung involvement, in order to avoid subjecting a patient to aggressive diagnostic tests, at least in the initial stages.

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.

Mediterranean diet and asthma in Spanish schoolchildren.

There is still debate on the effect of dietetic factors on the prevalence or severity of asthma, as well as the interaction with other factors. We have analysed the prevalence and severity of asthma according to adherence to the Mediterranean diet (MD), its association with obesity and family life style. We performed a cross-sectional study on 14,700 children and adolescents in six health areas in our region. We used the International Study of Asthma and Allergies in Childhood questionnaire to collect asthma symptoms, dietary habits, anthropometric parameters, parental smoking habits and maternal education level. The diet pattern was analysed using a Mediterranean Diet Score. In the logistic regression we analysed the influence of adhering to the MD on the prevalence and severity of asthma, adjusted for the other parameters included. Greater adherence to the MD is associated with a higher risk of severe asthma (odds ratios = 2.26, 95% CI: 1.21-4.22) in girls of 6-7 yr. There was no significant relationship for the other asthma categories in the population studied. The results of our study do not support a protective effect of the MD on the prevalence or severity of asthma.

Diagnostic value of interleukin-12 p40 in tuberculous pleural effusions.

The diagnosis of tuberculous pleural effusion (TBPE) is frequently problematic. Several markers of TBPE in pleural fluid have been evaluated, with different results. Pleural effusions from 96 patients were classified on the basis of definitive diagnosis as tuberculous (n = 39), neoplastic (n = 42) or parapneumonic (n = 15). Adenosine deaminase (ADA), ADA isoform ADA-2, interferon (IFN)-gamma, CD3(+)/DR(+) T-lymphocytes and interleukin (IL)-12 p40 were determined in all 96 effusions. The efficiency of IL-12 p40 for diagnosis of TBPEs was evaluated, in comparison with those of the other parameters, by comparing the areas under their receiver operating characteristics. With the threshold value of 550 pg.mL(-1), IL-12 p40 had a sensitivity of 92.3% (36 out of 39) and specificity of 70.2% (17 false positives). The misclassification rate of IL-12 p40 was significantly greater than those of ADA-2 and ADA. Among TBPEs, ADA correlated significantly with ADA-2, and IFN-gamma with ADA and IL-12 p40. Although tuberculous pleural effusions show values of interleukin-12 p40 that are significantly higher than neoplastic and parapneumonic fluids, this parameter is less efficient than adenosine deaminase, adenosine deaminase isoform 2 and interferon-gamma. Its routine determination is, accordingly, not justified.

Young man with asthma and infertility.

Asthma and male infertility are common diseases that can occur in the same patient. In some cases they could have patho-physiological changes common to both diseases. Our patient was seen as a result of having an irritating cough with wheezing, mainly at night, for more than a month. Asthma was diagnosed, and he responded favourably to the treatment given. Upon being informed that he had been examined for infertility for 5 years, alpha-1 antitrypsin (AAT) levels were requested. These confirmed that he had a phenotype SZ AAT deficiency. These findings, together with some evidence published recently, suggested that there is a need to rule out AAT deficiency in males with asthma and infertility.

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.

Exposure to furry pets and the risk of asthma and allergic rhinitis: a meta-analysis.

BACKGROUND: Exposure to pets has been implicated as a risk factor for asthma. However, this relation has been difficult to assess in individual studies because of the large potential of selection bias. We sought to examine the association between exposure to furry pets and asthma and allergic rhinitis by means of a meta-analysis. METHODS: We retrieved studies published in any language by searching systematically Medline (1966-March 2007), Embase, LILACS and ISI Proceedings computerized databases, and by examining manually the references of the original articles and reviews retrieved. We included cohort and case-control studies reporting relative risk estimates and confidence intervals of exposure to cats, dogs and unspecified furry animals and subsequent asthma and allergic rhinitis. We excluded cross-sectional studies and those studies that did not measure exposure but rather sensitization to pets. RESULTS: Thirty-two studies were included. For asthma, the pooled relative risk related to dog exposure was 1.14 (95% CI 1.01-1.29), that related to exposure to any furry pet was 1.39 (95% CI 1.00-1.95). Among cohort studies, exposure to cats yielded a relative risk of 0.72 (95% CI 0.55-0.93). For rhinitis, the pooled relative risk of exposure to any furry pet was 0.79 (95% CI 0.68-0.93). CONCLUSIONS: Exposure to cats exerts a slight preventive effect on asthma, an effect that is more pronounced in cohort studies. On the contrary, exposure to dogs increases slightly the risk of asthma. Exposure to furry pets of undermined type is not conclusive. More studies with exact measurement of exposure are needed to elucidate the role of pet exposures in atopic diseases.