Is asthma a risk factor for COVID-19? Are phenotypes important?

Asthma is a major health problem all over the world [1]. Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen, it is important to quantify the risk that the current coronavirus disease 2019 (COVID-19) pandemic may represent for patients with asthma. These results reaffirm the idea that asthma does not appear to be a risk factor for the development of #COVID19. However, most of the asthma patients in this study had a non-T2 phenotype

Diagnosis and follow up of chronic hypersensitivity pneumonitis: utility of non-invasive measurement of airway inflammation /

La NH, también conocida como alveolitis alérgica extrínseca, cursa con una desestructuración del parénquima pulmonar, como resultado de una respuesta inflamatoria de causa inmunológica, secundaria a una inhalación repetida de un antígeno, generalmente de carácter orgánico, al que previamente el individuo se ha sensibilizado. Un reconocimiento progresivo de la ubicuidad de estos antígenos en el medio ambiente y la mejora de las herramientas diagnósticas ha permitido un incremento de los diagnósticos de NH tanto en el medio doméstico como en el ocupacional. La patología típicamente se caracteriza por una alveolitis linfocítica y una neumonitis granulomatosa en el estudio histológico. La NH sigue suponiendo un reto diagnóstico para los facultativos que se dedican a estudiar esta patología, debido al amplio espectro de hallazgos clínicos y la falta de un "gold standard" para realizar un diagnóstico preciso. El diagnóstico depende de una fuerte sospecha diagnóstica inicial, una exhaustiva historia clínica que tenga en cuenta todas las posibles exposiciones, junto con la integración de hallazgos inmunológicos, radiológicos, y el estudio anatomopatológico de la biopsia pulmonar. Puesto que se trata de una enfermedad inmunológica, parece lógico pensar que el mejor método diagnóstico para la misma sea una prueba diagnóstica de carácter inmunológico, como el SIC, cuyo objetivo es reproducir en una cabina de provocación en el laboratorio, la exposición antigénica que produce la patología y objetivar en este contexto cambios clínicos, analíticos y de función pulmonar en condiciones de seguridad. Sin embargo, en la actualidad se carece de unos criterios homogéneos para el diagnóstico de NH tanto a nivel de la inhalación del antígeno como de evaluación de la positividad de la prueba. Además la sensibilidad y especificidad del SIC es del 85 y 86% respectivamente, de forma que un resultado negativo no descarta la NH. Por ello el objetivo de los dos primeros estudios de la presente tesis fue estudiar los cambios de los valores del pH del AEC y del FeNO antes y después del SIC en pacientes con sospecha de NH crónica y analizar su posible utilidad para mejorar la rentabilidad del SIC, así como valorar su potencial uso como marcadores inflamatorios en NH crónica. El primer capítulo de esta tesis confirmó que el pH del AEC podría ser de utilidad para el diagnóstico de NH crónica y que podría disminuir el número de falsos negativos del SIC. Una caída del pH del AEC de 0,4 después del SIC tiene una especificada del 100% para el diagnóstico de NH crónica por hongos. El segundo capítulo de la presente tesis reveló que el FeNO no parece ser de utilidad para el diagnóstico de NH crónica. Otra de las incógnitas de la NH crónica estriba en su evolución, ya que si bien varios autores sostienen que la NH es una enfermedad de evolución favorable, esta afirmación probablemente solo es aplicable a las formas agudas y subagudas de la patología. La mayoría de estudios que evalúan la supervivencia de la NH no diferencian entre las distintas formas de presentación de esta patología (aguda, subaguda y crónica) y los resultados de los diferentes estudios difieren sustancialmente en cuanto a los resultados. Por tanto el tercer capítulo de esta tesis tuvo por objetivo determinar la supervivencia y los principales factores pronósticos de la NH crónica, en la serie de pacientes más extensa recogida hasta la fecha. Este estudio reveló una mediana de supervivencia de 7 años desde el diagnóstico. La TLC, DLCO y el recuento de linfocitos en el BAL se asociaron de forma independiente a la mortalidad de estos pacientes y la FVC y la DLCO iniciales fueron los predictores de la tasa anual de pérdida de función pulmonar.Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is characterised by a destructuring of the pulmonary parenchyma, as a result of an immunological inflammatory response, following the repeated inhalation of an antigen, generally of an organic nature, to which the individual had previously become sensitised. A progressive acknowledgment of the ubiquity of these antigens in the environment and the improvement of diagnostic tools has led to an increase in the diagnosis of HP both in the domestic and occupational settings. The pathology is typically characterised by lymphocytic alveolitis and granulomatous pneumonitis in the histological study. HP continues to be a diagnostic challenge for doctors studying this pathology, due to the wide spectrum of clinical findings and the lack of a "gold standard" to perform an accurate diagnosis. The diagnosis depends on a strong initial diagnostic suspicion, an exhaustive clinical record that considers all possible exposures, and the incorporation of immunological and radiological findings and the anatomopathological study of pulmonary biopsy. Since it is an immunological disease, it seems logical to think that the best diagnostic method for same would be an immunological-type diagnosis test, such as SIC, which seeks to reproduce the antigen exposure that produces the disease in a provocation cabin in a laboratory, and present in this context clinical, analytical and pulmonary function changes in safe conditions. However, at present there is a lack of homogeneous criteria to diagnose HP, both in terms of inhalation of the antigen and evaluation of the test positivity. Moreover, the sensitivity and specificity of the SIC is 85 and 86% respectively, and as such, a negative result does not rule HP out. Therefore, the aim of the first two studies in the present thesis was to study the changes in the pH values of the AEC and FeNO prior to and following the SIC in patients with suspected chronic HP, and to analyse their possible role in improving the usefulness of SIC, as well as to assess their potential use as inflammatory markers in chronic HP. The first chapter of this thesis confirmed that the pH of the AEC could be useful in the diagnosis of chronic HP and could reduce the number of false negatives in the SIC. A 0.4 drop in the pH of AEC following the SIC has a 100% specificity for the diagnosis of chronic HP caused by fungus. The second chapter of this thesis revealed that FeNO does not appear to be useful in the diagnosis of chronic HP. Another unknown factor of chronic HP lies in its progression, since although various authors maintain that HP is a disease with a favourable progression, this statement probably only applies in the acute and subacute forms of the disease. The majority of studies assessing the survival rate of HP do not differentiate between the different ways in which the disease can manifest (acute, subacute and chronic) and the results of the different studies differ considerably in terms of outcomes. Therefore, the third chapter of this thesis sought to determine the survival and main prognostic factors of chronic HP, in the largest series of patients used to date. This study revealed an average survival rate of 7 years from diagnosis. The TLC, DLCO and the lymphocyte in the BAL were independently associated with the mortality of these patients, and the initial FVC and DLCO were predictors of the annual loss in pulmonary function

Characteristics and treatment patterns of patients with asthma on multiple-inhaler triple therapy in Spain

The aim of this observational, retrospective study was to describe characteristics, treatment patterns, and adherence among patients with asthma who initiated multiple-inhaler triple therapy (MITT) in Catalonia, Spain. This study used data of patients initiating MITT in 2016 from the SIDIAP (Information System for Research in Primary Care) database, which covers ~80% of the Catalonian population (5.8 million). Of 1,204 patients initiating MITT, 361 (30.0%) stepped down (discontinued ≥ 1 and continued ≥1 MITT component) and 89 (7.4%) stopped all three components of MITT for a period of 60 days during the following 12 months. In the follow-up period, 196 (16.3%) patients were considered adherent to MITT (>0.8 proportion of days covered [PDC]), with a mean (standard deviation) PDC of 0.52 (0.51) days. Given the low adherence and substantial rates of step down/discontinuation among patients initiating MITT, there is an urgent need to implement strategies to improve treatment adherence/persistence

Is asthma a risk factor for COVID-19? Are phenotypes important?

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Infeccions respiratòries i tuberculosi; Asma i al·lèrgiaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; COVID-19; Infecciones respiratorias y tuberculosis; Asma y alergiaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Respiratory infections and tuberculosis; Asthma and allergyThese results reaffirm the idea that asthma does not appear to be a risk factor for the development of #COVID19. However, most of the asthma patients in this study had a non-T2 phenotype

Results of a Phase 2b Trial With GB001, a Prostaglandin D2 Receptor 2 Antagonist, in Moderate to Severe Eosinophilic Asthma

Asthma; Asthma worsening; Eosinophilic asthmaAsma; Empitjorament de l'asma; Asma eosinofílicaAsma; Empeoramiento del asma; Asma eosinofílicaBackground Prostaglandin D2 receptor 2 (DP2) antagonists inhibit prostaglandin D2-induced effects, including recruitment and activation of cells driving asthma pathogenesis. However, challenges identifying target population and end points persist. Research Question What is the effect of the DP2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma? Study Design and Methods In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count ≥ 250 cells/μL. Patients aged ≥ 18 years to < 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment. Results A total of 480 patients were treated. The ORs for asthma worsening for GB001 20 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, and GB001 40 mg. Interpretation Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury.This work was supported by GB001, Inc., a wholly owned subsidiary of Gossamer Bio, Inc

Risk factors for the development of bronchiectasis in patients with asthma

Asthma; Medical researchAsma; Investigación médicaAsma; Recerca mèdicaThough asthma and bronchiectasis are two different diseases, their coexistence has been demonstrated in many patients. The aim of the present study is to compare the characteristics of asthmatic patients with and without bronchiectasis and to assess risk factors for the development of this condition. Two hundred and twenty-four moderate-severe asthmatic patients were included. The severity of bronchiectasis was assessed by Reiff and FACED parameters. Logistic regression was used to identify independent factors associated with bronchiectasis. Bronchiectasis was identified in 78 asthma patients. In severe asthma patients, its prevalence was 56.9%. Bronchiectasis was defined as mild in81% of patients using modified Reiff criteria and in 74% using FACED criteria. Asthmatic patients with bronchiectasis had decreasing FEV1, FVC and FEV1/FVC (p = 0.002, 0.005 and 0.014 respectively), presented more frequent asthma exacerbations (p < 0.001) and worse asthma control (ACT 21 vs 16pts, p < 0.001). Factors independently associated with bronchiectasis were older age (42–65 years: OR, 3.99; 95% CI 1.60 to 9.95, P = 0.003; ≥ 65 years: OR, 2.91; 95% CI 1.06 to 8.04, P = 0.039), severe asthma grade (OR, 8.91; 95% CI 3.69 to 21.49; P < 0.001) and frequency of asthma exacerbations (OR, 4.43; 95% CI 1.78 to 11.05; P < 0.001). In patients with severe asthma, age of asthma onset (OR, 1.02; 95% CI 1.01 to 1.04; P = 0.015) and asthma exacerbations (OR, 4.88; 95% CI 1.98 to 12.03; P = 0.001) were independently associated with the development of bronchiectasis. The prevalence of bronchiectasis in severe asthmatic patients is high. Age of asthma onset and exacerbations were independent factors associated with the occurrence of bronchiectasis.The study was partially supported by FIS PI15/01900 (Fondo Europeo de Desarrollo Regional (FEDER) and Fundacio Catalana de Pneumología (FUCAP). MJC is supported by the Miguel Servet program of the Instituto de Salud Carlos III (MSII17/00025). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Criptococosis pulmonar que simula un cáncer de pulmón

Cryptococcosis; Pulmonary malignancyCriptococcosi; Càncer de pulmóCriptococosis; Cáncer de pulmó

Sensitization to avian and fungal proteins in different work environments

Birds; Fungi; Hypersensitivity pneumonitisOcells; Fongs; Pneumonitis per hipersensibilitatAves; Hongos; Neumonitis por hipersensibilidadIntroduction Hypersensitivity pneumonitis (HP) is usually caused by the inhalation of avian and fungal proteins. The present study assesses a cohort of Urban Pest Surveillance and Control Service (UPSCS) workers with high exposure to avian and fungal antigens, in order to identify their degree of sensitization and the potential risk of developing HP. Methods Workers were divided according to their work activity into Nest pruners (Group 1) and Others (Group 2). All individuals underwent a medical interview, pulmonary function tests and the determination of specific IgG antibodies. Antigenic proteins of pigeon sera were analysed using two-dimensional immunoblotting. Proteins of interest were sequenced by liquid-chromatography–mass spectrometry (LC–MS). Results 101 workers were recruited (76 men, average age: 42 yrs); (Group 1 = 41, Group 2 = 60). Up to 30% of the study population exhibited increased levels of IgGs to pigeon, small parrot and parrot, and up to 60% showed high levels of Aspergillus and Penicillium IgGs. In Group 1, specific parakeet and Mucor IgGs were higher (p = 0.044 and 0.003 respectively) while DLCO/VA% were lower (p = 0.008) than in Group 2. Two-dimensional immunoblotting showed protein bands of 20–30 KDa recognized by HP patients but not by workers. LC–MS analysis identified Ig Lambda chain and Apolipoprotein A-I as candidate proteins for distinguishing HP patients from exposed workers. Conclusions Two pigeon proteins were identified that may play a role in the development of pathological differences between HP patients and exposed workers. DLCO/VA may have a predictive value in the development of HP disease.SSD is a researcher supported by CIBER, MJC is supported by the Miguel Servet program of the Instituto de Salud Carlos III (MSII17/00025) and IO is a researcher supported by the Pla Estrategic de Recerca i Innovaci en Salut (PERIS) 2016–2020 (SLT008/18/00108; G60594009). This project received funding from FIS PI PI15/01954, Fondo Europeo de Desarrollo Regional (FEDER), Fundació Catalana de Pneumologia (FUCAP) and Sociedad Española de Patología respiratoria (SEPAR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Influence of the environment on the characteristics of asthma

Environmental sciences; Health careCiències ambientals; Atenció sanitàriaCiencias Ambientales; Atención sanitariaFew studies have compared the prevalence of asthma in urban and rural settings or explored the issue of whether these two manifestations of the disease may represent different phenotypes. The aim of this study was: (a) to establish whether the prevalence of asthma differs between rural and urban settings, and b) to identify differences in the clinical presentation of asthma in these two environments. Descriptive epidemiological study involving individuals aged 18 or over from a rural (n = 516) and an urban population (n = 522). In the first phase, individuals were contacted by letter in order to organize the administration of a first validated questionnaire (Q1) designed to establish the possible prevalence of bronchial asthma. In the second phase, patients who had presented association patterns in the set of variables related to asthma in Q1 completed a second validated questionnaire (Q2), designed to identify the characteristics of asthma. According to Q1, the prevalence of asthma was 15% (n = 78) and 11% (n = 59) in rural and urban populations respectively. Sixty-five individuals with asthma from the rural population and all 59 individuals from the urban population were contacted and administered the Q2. Thirty-seven per cent of the individuals surveyed had previously been diagnosed with bronchial asthma (35% in the rural population and 40% in the urban setting). In the urban asthmatic population there was a predominance of women, a greater personal history of allergic rhinitis and a family history of allergic rhinitis and/or eczema. Asthma was diagnosed in adulthood in 74.8% of the patients, with no significant differences between the two populations. Regarding symptoms, cough (morning, daytime and night) and expectoration were more frequent in the urban population. The prevalence of asthma does not differ between urban and rural settings. The differences in exposure that characterize each environment may lead to different manifestations of the disease and may also affect its severity.MJC is supported by the Miguel Servet program of the Instituto de Salud Carlos III (MSII17/00025). This project received funding from the Fundació Catalana de Pneumologia (FUCAP), FIS PI18/00344, Fondo Europeo de Desarrollo Regional (FEDER) and Menarini. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Aeroallergen sensitisation for detecting asthma in primary care:a diagnostic test accuracy study

peer reviewe