Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study.

OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

Menopause Is Associated with Accelerated Lung Function Decline.

RATIONALE: Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. OBJECTIVES: To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause. METHODS: The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. MEASUREMENTS AND MAIN RESULTS: Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. CONCLUSIONS: Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

The Response to Biologics is Better in Patients with Severe Asthma Than in Patients with Asthma-COPD Overlap Syndrome.

Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma-COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months. Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with ≥1 exacerbation and ≥1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of "controlled" patients (with no exacerbations, no need for corticosteroids and ACT ≥ 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients.

Residential surrounding greenspace and age at menopause: A 20-year European study (ECRHS).

BACKGROUND: Menopause is associated with a number of adverse health effects and its timing has been reported to be influenced by several lifestyle factors. Whether greenspace exposure is associated with age at menopause has not yet been investigated. OBJECTIVE: To investigate whether residential surrounding greenspace is associated with age at menopause and thus reproductive aging. METHODS: This longitudinal study was based on the 20-year follow-up of 1955 aging women from a large, population-based European cohort (ECRHS). Residential surrounding greenspace was abstracted as the average of satellite-based Normalized Difference Vegetation Index (NDVI) across a circular buffer of 300 m around the residential addresses of each participant during the course of the study. We applied mixed effects Cox models with centre as random effect, menopause as the survival object, age as time indicator and residential surrounding greenspace as time-varying predictor. All models were adjusted for smoking habit, body mass index, parity, age at menarche, ever-use of contraception and age at completed full-time education as socio-economic proxy. RESULTS: An increase of one interquartile range of residential surrounding greenspace was associated with a 13% lower risk of being menopausal (Hazard Ratio: 0.87, 95% Confidence Interval: 0.79-0.95). Correspondingly the predicted median age at menopause was 1.4 years older in the highest compared to the lowest NDVI quartile. Results remained stable after additional adjustment for air pollution and traffic related noise amongst others. CONCLUSIONS: Living in greener neighbourhoods is associated with older age at menopause and might slow reproductive aging. These are novel findings with broad implications. Further studies are needed to see whether our findings can be replicated in different populations and to explore the potential mechanisms underlying this association.

Exogenous female sex steroids may reduce lung ageing after menopause: A 20-year follow-up study of a general population sample (ECRHS).

OBJECTIVES: Menopause involves hypoestrogenism, which is associated with numerous detrimental effects, including on respiratory health. Hormone replacement therapy (HRT) is often used to improve symptoms of menopause. The effects of HRT on lung function decline, hence lung ageing, have not yet been investigated despite the recognized effects of HRT on other health outcomes. STUDY DESIGN: The population-based multi-centre European Community Respiratory Health Survey provided complete data for 275 oral HRT users at two time points, who were matched with 383 nonusers and analysed with a two-level linear mixed effects regression model. MAIN OUTCOME MEASURES: We studied whether HRT use was associated with the annual decline in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). RESULTS: Lung function of women using oral HRT for more than five years declined less rapidly than that of nonusers. The adjusted difference in FVC decline was 5.6 mL/y (95%CI: 1.8 to 9.3, p = 0.01) for women who had taken HRT for six to ten years and 8.9 mL/y (3.5 to 14.2, p = 0.003) for those who had taken it for more than ten years. The adjusted difference in FEV1 decline was 4.4 mL/y (0.9 to 8.0, p = 0.02) with treatment from six to ten years and 5.3 mL/y (0.4 to 10.2, p = 0.048) with treatment for over ten years. CONCLUSIONS: In this longitudinal population-based study, the decline in lung function was less rapid in women who used HRT, following a dose-response pattern, and consistent when adjusting for potential confounding factors. This may signify that female sex hormones are of importance for lung ageing.

[Tobacco smoking and sputum smear conversion in pulmonary tuberculosis]. / Tabaquismo y negativización bacteriológica del esputo en la tuberculosis pulmonar.

BACKGROUND AND OBJECTIVE: To analyze if cigarette smoking delays the sputum smear conversion in pulmonary tuberculosis. PATIENTS AND METHOD: Ninety eight patients were diagnosed with pulmonary tuberculosis. Patients were all not immunosuppressed, infected by human immunodeficiecy virus (HIV) or drug resistant. Sixty four of them were smokers with a pack-year index (standard deviation) of 33.69 (23.12). Delayed sputum smear conversion (DC) was considered when 2 positive sputum culture results were obtained in the second month of anti-tuberculous treatment and was associated with the following variables in 2 groups: a) total group (in which all the patients were included): age, sex, smoking habits, risk factors (alcohol consumption, diabetes mellitus, immunosuppression, drug addicion, malnutrition), time with symptoms, radiologic presentation and bacterial load, and b) smokers: age, sex, risk factors, time with symptoms, radiologic presentation, bacterial load and pack-year index. For the statistical analysis, chi2 test, Student t test and logistic regression model were used, considering the dependant variable DC. RESULTS: In the total group, 17 patients (17.3%) had DC, 16 of them had a history of smoking and in the univariate analysis it was associated with: alcohol consumption, time with symptoms, radiologic presentation as bilateral cavitary infiltrates and smoking habits. The logistic regression analysis showed an association with smoking habits (odds ratio = 9.8; p = 0.03) and bilateral cavitary infiltrates (odds ratio = 3.61; p = 0.02). In the group of smokers, DC was associated in the univariate analysis with the female sex. CONCLUSIONS: Smoking habits delay sputum conversion in patients with pulmonary tuberculosis not associated with HIV and non-resistant bacilli. According to these results it is necessary to assist smoking cessation in patients who are receiving antituberculous treatment.

[Chemotherapy and survival in advanced non-small cell lung carcinoma: is pneumologists' skepticism justified?]. / Quimioterapia y supervivencia en el carcinoma broncogénico no microcítico en estadios avanzados: 'está justificado el nihilismo de los neumólogos?

OBJECTIVE: Few studies have assessed whether the advantage chemotherapy has been shown to have in treating advanced non-small lung carcinoma in clinical trials is transferrable to normal health care activity. This could explain the skepticism of a large number of pneumologists towards this treatment. The objective of our study was to analyze prognostic factors related to survival and to see whether cytostatic treatment was an independent predictor. PATIENTS AND METHODS: Patients enrolled in the study had been diagnosed with non-small cell carcinoma in stages IV or IIIB with pleural or N2-N3 involvement and with a performance status of 2 or below according to the Eastern Cooperative Oncology Group (ECOG). Survival was analyzed with regard to the following variables: age, sex, comorbidity, weight loss, laboratory test results, histological type, ECOG score, TNM staging, and treatment. The Student t test, the chi(2) test, the Kaplan-Meier method, the log-rank test, and Cox regression analysis were used in the statistical analysis. RESULTS: We enrolled 190 patients (157 men and 33 women) with a mean (SD) age of 61.75 (10.85) years (range, 33-85 years). Of these patients, 144 received cytostatic treatment and 46 palliative treatment. The median survival was 31 weeks and was related to absence of weight loss (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.26-2.39; P=.001), cytostatic treatment (HR, 1.85; 95% CI, 1.25-2.76; P=.002), and ECOG score of 0 to 1 (HR, 2.84; 95% CI, 1.62-5.00; P=.0001). In patients with ECOG scores of 0 to 1, weight loss and treatment were significant prognostic factors. Survival in the ECOG 2 group was 15 weeks for patients undergoing cytostatic treatment and 11 weeks for patients with symptomatic treatment. CONCLUSIONS: In normal clinical practice, chemotherapy significantly prolongs survival in patients with performance status of less than 2, more time being gained if there is no associated weight loss. We conclude that the reluctance shown by many pneumologists toward using this treatment is not entirely justified.

[Treatment and course of community-acquired pneumonia caused by atypical pathogens]. / Neumonía adquirida en la comunidad por gérmenes atípicos: tratamiento y evolución.

OBJECTIVE: To study the course of disease and outcomes in a group of patients with community-acquired pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella species ,Coxiella burnetii, and Chlamydophila pneumoniae) according to the empiric treatment received. PATIENTS AND METHODS: Of a total of 390 patients admitted to our hospital with pneumonia between January 1996 and February 2001, the causative microorganism was an atypical pathogen in 89 cases. Patients were divided retrospectively into 2 groups according to the empiric treatment they received: group A, who had received an antibiotic regime (quinolones or macrolides) that provided coverage for atypical pathogens; and group B, who had received treatment that did not provide such coverage. Clinical course was assessed in terms of the differences between the 2 groups in length of hospital stay, radiographic resolution, readmission at 30 days after discharge, and mortality. RESULTS: A total of 89 patients with pneumonia caused by atypical pathogens (39 in group A and 50 in group B) were studied. No significant between-group differences in the variables were found. CONCLUSIONS: In this group of patients hospitalized for community-acquired pneumonia, antibiotic regimens providing coverage for atypical pathogens did not improve either clinical or radiographic evolution.

[Community-acquired pneumonia: serum adenosine-deaminase activity in the aetiological diagnosis]. / Neumonía adquirida en la comunidad: adenosindesaminasa plasmática como marcador etiológico.

BACKGROUND: Adenosine deaminase (ADA) is a cytoplasmic enzyme which activity is increased in disorders that stimulate cells involved in the immune system. In community-acquired pneumonia (CAP), increased levels of serum ADA have been associated with the presence of atypical microorganisms as the source of the former. Previous studies have shown ADA increases in non-infectious diseases. We evaluated the factors that may influence plasmatic ADA (ADAp) levels in CAP patients. PATIENTS AND METHODS: A study with cases (245 episodes of CAP) and controls (49) was designed, and the differences in ADAp activity with regard to organisms, comorbidity factors and complications were analyzed. A logistic regression analysis was performed. RESULTS: CAP caused by atypical microorganisms were found to have increased ADAp values. Variables that independently increased ADAp levels were: atypical etiology (OR = 5.9), liver disease (OR = 5.8), diabetes mellitus (OR = 1.9), and prior antibiotic consumption (OR = 1.7). CONCLUSIONS: ADAp is an etiologic marker that could be useful in the empiric approach of the treatment of CAP.

Prevalence of chronic obstructive pulmonary disease in the Canary Islands.

INTRODUCTION: The prevalence of chronic obstructive pulmonary disease (COPD) varies significantly among the different geographical areas reported. In Spain, two epidemiological studies have shown a prevalence of 9-10% in the population aged over 40. However, neither of these studies included the Canary Islands, which are of interest due to their climatic conditions and high incidence of smoking. MATERIALS AND METHODS: A random group of 1,353 subjects aged between 40 and 70years was selected from a sample population of 596,478 individuals. Participants completed a questionnaire and then performed spirometry with bronchodilator testing if obstruction was observed. COPD was diagnosed when the post-bronchodilator FEV1/FVC ratio was less than 0.70. RESULTS: The prevalence of COPD was 7.3% (95%CI: 5.5-9.5) and was higher in males than in females (8.7% vs. 6.3%, P=.134). The incidence of smoking was 29.4% (95%CI: 25.4-33.1) and was also higher in males than in females (35.1% vs 25.4%, P<.001). The prevalence of COPD stratified by severity of obstruction, according to the GOLD criteria, was 16% in groupi, 69.9% in groupii, 10.4% in groupiii and 3.3% in groupiv. 71.6% of the subjects were underdiagnosed and 63.5% undertreated. CONCLUSIONS: Despite having one of the highest rates of smoking in Spain, the prevalence of COPD in the Canary Islands is lower than in most of the Spanish regions studied.

The Spanish Society of Pulmonology and Thoracic Surgery Lung Cancer Cooperative Group-II registry. A descriptive study.

INTRODUCTION AND OBJECTIVES: The seventh edition of the TNM classification, together with undeniable advantages, has limitations. The International Association for the Study of Lung Cancer (IASLC) Staging Committee has designed an international prospective study to improve this classification. A group of thoracic surgeons and pulmonologists was established in the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) Oncology area, and created a registry of new lung cancer (LC) cases to participate in this project. The aim of this paper is to describe the main characteristics of the patients included. MATERIALS AND METHODS: Prospective, observational, multicentre, multiregional data collection (epidemiological, clinical, therapeutic and, especially, anatomical extension) study, according to the IASLC protocol, to analyse its prognostic value. RESULTS: Two thousand, four hundred and nineteen patients (83.6% men) from 28 hospitals were included. Ninety-six percent of the men and 54% of the women were smokers or ex-smokers. Chest/abdominal computed tomography (CT) scanning was performed in over 90% and positron emission tomography (PET)/CT scanning in 51.5% of cases. Among the 1035 patients who underwent surgery, 77% had early stages (ia to iib), and 61.6% of those treated using other methods had stage iv. Respiratory comorbidity was higher in men (47.9% versus 21.4%). The most common histological subtype was adenocarcinoma (34%), especially in non-smoking women (69.5%). CONCLUSIONS: The proportion of women and adenocarcinomas, as well as those resected at an early stage, increased among LC cases in Spain.