Sensitization to avian and fungal proteins in different work environments.

INTRODUCTION: 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.

The Role of Inflammatory Phenotype in Patients With Exacerbation-prone Asthma and Ongoing Therapy

Introduction: The risk factors for having frequent exacerbations are not well documented in cohort studies of patients with asthma on existing therapy. The objective of the present study was to compare the clinical and inflammatory characteristics of patients with exacerbation-prone asthma (EPA) with a history of two or more exacerbations in the previous year with those who had presented just one or no exacerbation. Methods: An ambispective observational study was conducted in a tertiary hospital. Patients diagnosed with moderate or severe asthma and ongoing therapy, whose inflammatory profile was determined by means of allergy and atopy status, blood eosinophilia and induced sputum were included. Patients were classified according to the number of asthma exacerbations in EPA (≥2 exacerbations in the previous year) vs. non-exacerbators (≤1 exacerbation in the previous year). Clinical, lung function and inflammatory characteristics of the two groups were compared. Results: Three hundred ten patients were visited in the Asthma Unit in 2018 and the combination of atopy and allergy status, blood eosinophilia and induced sputum was obtained in 96 (31%) patients. Of this latter group, 46 patients (47%) presented EPA compared to 50 (53%) non-exacerbators. Airway and blood eosinophilic inflammation did not differ between EPA and non-exacerbators in patients with asthma and ongoing therapy, and it was not a risk factor for EPA in our cohort. Conclusion: Airway or blood type 2 inflammation status is not a valid tool for recognizing EPA or predicting asthma exacerbations in asthma patients following controller therapy. (AU)

The Role of Inflammatory Phenotype in Patients With Exacerbation-prone Asthma and Ongoing Therapy.

INTRODUCTION: The risk factors for having frequent exacerbations are not well documented in cohort studies of patients with asthma on existing therapy. The objective of the present study was to compare the clinical and inflammatory characteristics of patients with exacerbation-prone asthma (EPA) with a history of two or more exacerbations in the previous year with those who had presented just one or no exacerbation. METHODS: An ambispective observational study was conducted in a tertiary hospital. Patients diagnosed with moderate or severe asthma and ongoing therapy, whose inflammatory profile was determined by means of allergy and atopy status, blood eosinophilia and induced sputum were included. Patients were classified according to the number of asthma exacerbations in EPA (≥2 exacerbations in the previous year) vs. non-exacerbators (≤1 exacerbation in the previous year). Clinical, lung function and inflammatory characteristics of the two groups were compared. RESULTS: Three hundred ten patients were visited in the Asthma Unit in 2018 and the combination of atopy and allergy status, blood eosinophilia and induced sputum was obtained in 96 (31%) patients. Of this latter group, 46 patients (47%) presented EPA compared to 50 (53%) non-exacerbators. Airway and blood eosinophilic inflammation did not differ between EPA and non-exacerbators in patients with asthma and ongoing therapy, and it was not a risk factor for EPA in our cohort. CONCLUSION: Airway or blood type 2 inflammation status is not a valid tool for recognizing EPA or predicting asthma exacerbations in asthma patients following controller therapy.

Disposition of Work-Related Asthma in a Spanish Asthma Cohort: Comparison of Asthma Severity Between Employed and Retired Workers.

BACKGROUND: Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma (WRA). Understanding the burden that WRA represents can help in the management of these patients. OBJECTIVE: To assess the influence of occupation on asthma in real life and analyze the characteristics of patients with WRA included in an asthma cohort. METHODS: This was a prospective multicenter study of a cohort of consecutive patients with asthma. A standardized clinical history was completed. Patients were classified as having WRA or non-WRA. All patients underwent respiratory function tests, FeNO test, and methacholine challenge (methacholine concentration that causes a 20% drop in FEV1) at the beginning of the study. They were classified into two groups, depending on their employment status: employed (group 1) or unemployed (group 2). RESULTS: Of the 480 patients included in the cohort, 82 (17%) received the diagnosis of WRA. Fifty-seven patients (70%) were still working. Mean age (SD) was 46 (10.69) years in group 1 and 57 (9.91) years in group 2 (P < .0001). Significant differences were observed in adherence to treatment (64.9% in group 1 vs 88% in group 2; P = .0354) and in severe asthma exacerbations (35.7% in group 1 vs 0% in group 2; P = .0172). No significant differences were observed in the rest of the variables analyzed. CONCLUSIONS: The burden of WRA in specialized asthma units is not negligible. The absence of differences in the severity of asthma, the treatment administered, alterations in lung function, and the number of exacerbations in those working versus not working may support the idea that advice regarding changing jobs should be customized for individual patients.

Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis.

INTRODUCTION: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. METHODS: We performed a multicentre prospective cohort study, including adult patients with asthma (N=512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. RESULTS: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. CONCLUSION: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps.

Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis.

Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins. The immunopathological pathways involved in the disease are still unknown. This study assesses the cellular immune response and the cytokine pattern in a mouse model of BRHP. On days -3 and -1, mice were intraperitoneally sensitized with commercial pigeon serum (PS) or saline. Intranasal instillations with PS or saline were carried out on three consecutive days/week over either 3 weeks (Group 1) or 12 weeks (Group 2). Leukocyte and cytokine patterns in lung tissue and pulmonary inflammation in bronchoalveolar lavage (BAL) were analysed. Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups. Group 1 had increased levels of eosinophils and T cells with reductions in neutrophils and B cells, while Group 2 showed high levels of B cells. Both groups exhibited increases in Th1 and Th2 cytokines. Group 2 also showed increased levels of IL-23, a Th17 cytokine. Increased levels of neutrophils, eosinophils and lymphocytes were observed in BAL samples of both groups compared with controls. In the first stages of BRHP, there is a mixed Th1/Th2 immune response, while during the progression of the disease, although there is a Th1 response, the cytokine levels seem to indicate a switch towards a Th2/Th17 mixed response.

Influence of the environment on the characteristics of asthma.

Few 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.

YKL-40 and KL-6 Levels in Serum and Sputum of Patients Diagnosed With Hypersensitivity Pneumonitis.

BACKGROUND: YKL-40 (chitinase 3-like-1) and Krebs von den Lungen-6 (KL-6) are 2 promising biomarkers that may have an important role in the management of interstitial lung diseases (ILD). OBJECTIVE: The aim of this study was to investigate the values of KL-6 and YKL-40 as biomarkers in the diagnosis and prognosis of patients with hypersensitivity pneumonitis (HP). METHODS: A cross-sectional study conducted in 49 patients diagnosed with HP due to exposure to birds (n = 32) or fungi (n = 17), 48 patients with other ILD, and 67 healthy volunteers. Patients with HP were divided into fibrotic and nonfibrotic. Serum and sputum YKL-40 and KL-6 levels were determined using commercial enzyme-linked immunosorbent assay kits. Receiver operating characteristic (ROC) curves were used to determine the sensitivity and specificity of both biomarkers for the diagnosis of HP. Pulmonary function tests were performed in patients during follow-up. RESULTS: KL-6 and YKL-40 levels were significantly higher in serum of patients with HP exposed to birds with a fibrotic pattern than in controls (P < .0001 and .0055, respectively). Serum KL-6 levels were also significantly higher in patients with fibrotic HP exposed to fungi compared with the control group (P = .0001). In patients with HP exposed to fungi, sputum KL-6 and YKL-40 levels were higher in those with a fibrotic pattern (P = .0289 and .016, respectively). ROC analysis showed that the range between 55-121 ng/mL for serum YKL-40 levels and 346-1441 U/mL for serum KL-6 levels had the best sensitivity and specificity for discriminating between patients with HP, healthy controls, and patients with idiopathic pulmonary fibrosis (IPF). In patients with HP, serum KL-6 levels correlated negatively with total lung capacity (r = -0.485; P = .0103) and diffusing capacity of the lungs for carbon monoxide (r = -0.534; P = .0002) at 12 months. CONCLUSIONS: Both KL-6 and YKL-40 proteins seem to be capable of distinguishing patients with HP from healthy individuals and from patients with IPF. Their sensitivity and specificity confirm their potential role as biomarkers. KL-6 may also be a predictor of disease progression.

Risk factors for the development of bronchiectasis in patients with asthma.

Though 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.

Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort.

INTRODUCTION: The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder. MATERIAL AND METHODS: We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients. RESULTS: When compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis. CONCLUSION: The MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities.

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

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. https://bit.ly/38hIp18.

Characterization of Occupational Eosinophilic Bronchitis in a Multicenter Cohort of Subjects with Work-Related Asthma Symptoms.

BACKGROUND: Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. OBJECTIVE: We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. METHODS: In this retrospective multicenter study, OEB was defined by (1) a fall in FEV1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness. RESULTS: An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). CONCLUSIONS: This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB.

ß2-agonistas en asma: el extraño caso del Dr. Jekyll y Mr. Hyde / ß2-Agonists in Asthma: The Strange case of Dr. Jekyll and Mr. Hyde

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