A 26-year-old female with steroid dependent eosinophilic asthma and nasal polyps who had successfully been treated with mepolizumab for 17 consecutive months with complete steroid withdrawal and symptoms control, stopped biologic treatment due to pregnancy efforts. Mepolizumab discontinuation resulted in frequent exacerbations and daily symptoms despite high dose ICS/LABA and re-initiation of oral steroids. Mepolizumab was initiated again, followed by improvement of asthma control and gradual withdrawal of steroids within 2 months. The patient became pregnant during the fourth month of mepolizumab re-initiation. The patient presented two asthma exacerbations during pregnancy treated with short course (3 days) oral steroids and delivery was uneventful (female, Apgar 9, weight 2750 g, length 59 cm) in week 40 by caesarean section.

The patient was a 70-year-old man with diabetes mellitus, alcoholic liver disease and bronchial asthma treated with corticosteroid and long-acting β-agonist inhalants. He had also been treated with nivolumab for advanced malignant melanoma for two years with a partial response. He presented to our department with intractable cough, which was attributed to uncontrolled bronchial asthma. Two weeks later, he presented with a high fever and worsened cough. He was diagnosed with bacterial pneumonia based on severe inflammation revealed by laboratory tests and right upper lung consolidation on chest radiography. Antibiotics via either oral or parenteral administration were ineffective and no pathogen was detected in sputum or blood cultures. Based on the air-crescent sign observed on chest computed tomography and a diffuse pseudomembranous lesion on the airway epithelium that was observed via bronchoscopy along with positive serum Aspergillus antigen, a clinical diagnosis of invasive pulmonary aspergillosis (IPA) was made and liposomal amphotericin B was initiated. Three days later, the patient developed massive hemoptysis, and he died of respiratory failure. Later, aspergillus-like mycelia were observed in the pathology of bronchial biopsy, supporting the clinical diagnosis of IPA. Although the use of immune checkpoint inhibitors has been reported to be beneficial for patients with some infectious diseases, it does not seem to be the case for patients with other infectious diseases including our patient.

BACKGROUND: Allergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs).
METHODS: REACT (Real world effectiveness in allergy immunotherapy) is a retrospective cohort study using claims data between 2007 and 2017. Study eligibility was a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analysed as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up (ClinicalTrial.gov: NCT04125888).
RESULTS: 46,024 AIT-treated subjects were matched with control subjects and 14,614 were included in the pre-existing asthma cohort. AIT-treated subjects were 29·5 (16·3) years and 53% were male. Compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in AR and asthma prescriptions, including both asthma controller and reliever prescriptions. Additionally, the AIT group had significantly greater likelihood of stepping down asthma treatment (P <0·0001). In addition to the reduction in asthma treatment in the AIT group, a greater reduction in severe asthma exacerbations was demonstrated (P<0·05). Reductions in pneumonia with antibiotic prescriptions, hospitalisations, and duration of inpatients stays were all in favour of AIT.
CONCLUSIONS: The study extends the existing RCT evidence for AIT by demonstrating longer-term and sustained effectiveness of AIT in the real world. Additionally, in patients with concurrent asthma, AIT was associated with reduced likelihood of asthma exacerbations and pneumonia.
BACKGROUND: The study was funded by ALK A/S.

BACKGROUND: Patients with pre-existing respiratory diseases in the setting of COVID-19 may have a greater risk of severe complications and even death.
METHODS: A retrospective, multicenter, cohort study with 5847 COVID-19 patients admitted to hospitals. Patients were separated in two groups, with/without previous lung disease. Evaluation of factors associated with survival and secondary composite end-point such as ICU admission and respiratory support, were explored.
RESULTS: 1,271 patients (22%) had a previous lung disease, mostly COPD. All-cause mortality occurred in 376 patients with lung disease (29.5%) and in 819 patients without (17.9%) (p < 0.001). Kaplan-Meier curves showed that patients with lung diseases had a worse 30-day survival (HR = 1.78; 95%C.I. 1.58-2.01; p < 0.001) and COPD had almost 40% mortality. Multivariable Cox regression showed that prior lung disease remained a risk factor for mortality (HR, 1.21; 95%C.I. 1.02-1.44; p = 0.02). Variables independently associated with all-cause mortality risk in patients with lung diseases were oxygen saturation less than 92% on admission (HR, 4.35; 95% CI 3.08-6.15) and elevated D-dimer (HR, 1.84; 95% CI 1.27-2.67). Age younger than 60 years (HR 0.37; 95% CI 0.21-0.65) was associated with decreased risk of death.
CONCLUSIONS: Previous lung disease is a risk factor for mortality in patients with COVID-19. Older age, male gender, home oxygen therapy, and respiratory failure on admission were associated with an increased mortality. Efforts must be done to identify respiratory patients to set measures to improve their clinical outcomes.
UNASSIGNED: Los pacientes con enfermedades respiratorias preexistentes pueden tener en el contexto de la covid-19 un mayor riesgo de complicaciones graves e incluso de muerte.
UNASSIGNED: Estudio de cohortes multicéntrico y retrospectivo de 5.847 pacientes con covid-19 ingresados en hospitales. Los pacientes se separaron en 2 grupos, sin y con enfermedad pulmonar previa. Se evaluaron factores asociados con la supervivencia y criterios combinados de valoración secundarios, como el ingreso en la UCI y la necesidad de asistencia respiratoria.
RESULTS: Mil doscientos setenta y un (1.271) pacientes (22%) tenían una enfermedad pulmonar previa, principalmente EPOC. La mortalidad por todas las causas ocurrió en 376 pacientes con enfermedad pulmonar (29,5%) y en 819 pacientes sin enfermedad pulmonar (17,9%; p < 0,001). Las curvas de Kaplan-Meier mostraron que los pacientes con enfermedades pulmonares tenían una peor supervivencia a los 30 días (HR: 1,78; IC del 95%: 1,58-2,01; p < 0,001) y la EPOC tenía una mortalidad de casi el 40%. La regresión de Cox multivariante mostró que la enfermedad pulmonar previa seguía siendo un factor de riesgo de mortalidad (HR: 1,21; IC del 95%: 1,02-1,44; p = 0,02). Las variables asociadas de forma independiente con el riesgo de muerte por todas las causas en pacientes con enfermedades pulmonares fueron la saturación de oxígeno inferior al 92% al ingreso (HR: 4,35; IC del 95%: 3,08-6,15) y el dímero D elevado (HR: 1,84; IC del 95%: 1,27-2,67). La edad menor de 60 años (HR: 0,37; IC del 95%: 0,21-0,65) se asoció con una disminución del riesgo de muerte.
CONCLUSIONS: La enfermedad pulmonar previa es un factor de riesgo de muerte en pacientes con covid-19. La edad avanzada, el sexo masculino, la oxigenoterapia domiciliaria y la insuficiencia respiratoria al ingreso se asociaron con un aumento de la mortalidad. Se deben realizar esfuerzos para identificar a los pacientes respiratorios y establecer medidas para mejorar sus resultados clínicos.

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 weeks, and an observational phase of 18-48 months. Two hundred participants were enrolled during three consecutive RSV seasons beginning in the fall of 2016 and were randomized to receive oral azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for an additional 7 days, or matched placebo. The study hypothesis is that in infants hospitalized with RSV bronchiolitis, the addition of azithromycin therapy to routine bronchiolitis care would reduce the likelihood of developing post-RSV recurrent wheeze (≥3 episodes). The primary clinical outcome is the occurrence of a third episode of wheezing, which is evaluated every other month by phone questionnaires and during yearly in-person visits. A secondary objective of the APW-RSV II clinical trial is to examine how azithromycin therapy changes the upper airway microbiome composition, and to determine if these changes are related to the occurrence of post-RSV RW. Microbiome composition is characterized in nasal wash samples obtained before and after the study treatments. This clinical trial may identify the first effective intervention applied during severe RSV bronchiolitis to reduce the risk of post-RSV RW and ultimately asthma.

OBJECTIVE: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients\' health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients.
METHODS: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients.
RESULTS: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945-2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06-0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15-0.24).
CONCLUSIONS: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients\' improvement.

UNASSIGNED: Severe asthma is a serious condition with a significant burden on patients\' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers\' specialty and experience.
UNASSIGNED: We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared.
UNASSIGNED: Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05).
UNASSIGNED: Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber\'s specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice.

Managing patients with severe asthma during the coronavirus pandemic and COVID-19 is a challenge. Authorities and physicians are still learning how COVID-19 affects people with underlying diseases, and severe asthma is not an exception. Unless relevant data emerge that change our understanding of the relative safety of medications indicated in patients with asthma during this pandemic, clinicians must follow the recommendations of current evidence-based guidelines for preventing loss of control and exacerbations. Also, with the absence of data that would indicate any potential harm, current advice is to continue the administration of biological therapies during the COVID-19 pandemic in patients with asthma for whom such therapies are clearly indicated and have been effective. For patients with severe asthma infected by SARS-CoV-2, the decision to maintain or postpone biological therapy until the patient recovers should be a case-by-case based decision supported by a multidisciplinary team. A registry of cases of COVID-19 in patients with severe asthma, including those treated with biologics, will help to address a clinical challenge in which we have more questions than answers.

BACKGROUND: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies.
OBJECTIVE: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort.
METHODS: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline.
RESULTS: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses.
CONCLUSIONS: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.

BACKGROUND: Both inflammatory and remodelling processes are associated with irreversible airway obstruction observed in severe asthma. Our aim was to characterize a group of severe asthmatic patients with or without persistent airway obstruction in relation to specific sputum inflammatory and remodelling biomarkers.
METHODS: Forty-five patients under regular high-dose inhaled corticosteroid/ß-2agonist treatment were studied, after a follow-up period of at least 2 years, with a minimum of 4 visits. Periostin, TGF-ß, RANTES, IL-8, GM-CSF, FGF-2, and cell counts were measured in induced sputum. Serum periostin was also measured.
RESULTS: Sputum induction was successfully performed in all but 5 patients. There were no significant differences in demographic and clinical data between patients with non-persistent obstruction (NO: FEV1/VC>88%pred.) and those with persistent obstruction (O: a not completely reversible obstruction with FEV1/VC<88%pred. at each visit before the study visit). Patients with persistent obstruction had significantly higher sputum periostin and TGF-ß concentrations than NO patients and a trend of higher serum periostin levels. GM-CSF and FGF-2 were significantly increased in NO compared to O patients. No differences between groups were found for RANTES, IL-8 and differential cell counts. Sputum periostin inversely correlated with functional parameters (prebronch. FEV1: rho = -0.36, p < 0.05; postbronch. FEV1: rho = -0.33, p = 0.05). Patients with high sputum periostin concentration (>103.3 pg/ml: median value) showed an absolute number of sputum eosinophils significantly higher than patients with low sputum periostin; this behavior was unobserved when serum periostin was considered.
CONCLUSIONS: Only periostin and TGF-ß identified a subgroup of severe asthmatic patients with persistent airway obstruction. Sputum periostin was also inversely associated with FEV1 and proved to be a more sensitive biomarker than serum periostin to identify severe asthmatics with higher sputum eosinophilia.