Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

PURPOSE: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. METHODS: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. RESULTS: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. CONCLUSIONS: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy.

A tailored approach to refractory severe Mepolizumab-associated headache: a case study.

INTRODUCTION: Biologic drugs have been shown to reduce asthma exacerbations, improve lung function and quality of life, reduce oral corticosteroid use in appropriately selected patients. Mepolizumab has been demonstrated to have a safety profile that is similar to placebo, however, when present side effects may lead to treatment discontinuation. Among these, headache is one of the most common. CASE STUDY: We hereby describe the case of a never-smoking male patient with an eosinophilic corticosteroid-dependent severe asthma. He displayed well controlled comorbidities and good adherence to the inhaled therapy. Mepolizumab was started in 2017 with an initial remarkable clinical improvement. After three doses of biologic therapy, he reported a severe orthostatic headache associated with vomiting, unresponsive to analgesic drugs, that required hospitalization. No other cause than treatment with Mepolizumab was found to be plausibly associated with this new-onset headache. The therapeutic regimen was modified by administering Mepolizumab for two consecutive months alternated with a one-month break. RESULTS: The patient did not experience any further episodes of headache, while maintaining a good and stable control of his asthma. We were able to taper oral corticosteroids, and no flares-ups occurred in the following 5 years. CONCLUSION: Our experience indicates that a tailored strategy for managing severe asthmatic patients, who have experienced side effects from biologic drugs, can be effective in maintaining drug efficacy while minimizing side effects. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes here described are replicable on a larger scale.

Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.

SARS-CoV-2 infection sequelae on exercise response: persistent or reversible? A 2-year perspective.

Post-COVID-19 exercise capacity sequalae on oxygen utilisation and ventilatory efficiency improve over time in most patients. Cardiopulmonary exercise testing is a valuable tool to identify those who may benefit from specific rehabilitative interventions. https://bit.ly/3qFd97x.

Does the severity of asthma affect exercise capacity and daily physical activity?

OBJECTIVE: Exercise capacity, daily physical activity, and psychological profile are crucial aspects in the management of asthmatic patients. Whether these features are expressed in a different way in mild-moderate (MMA) and severe asthma (SA) is unknown. METHODS: In this observational cross-sectional study, patients matching the American Thoracic Society/European Respiratory Society (ATS/ERS) definition for SA underwent incremental cardiopulmonary exercise testing (CPET), full lung function testing, and an evaluation of daily step count and physical activity. Questionnaires on quality of life, general fatigue, and presence of anxiety and depression traits (Hospital Anxiety and Depression Scale - HADS) were administered. Patients were compared with a cohort of age- and gender-matched MMA patients. RESULTS: We enrolled 16 SA, 17 MMA patients, and 16 healthy subjects. Compared to MMA, SA subjects showed a median (interquartile range) reduced peak oxygen consumption during CPET (20.4 (17.2-23.3) vs. 25.6 (18.5-30.3) ml/min/kg; p = 0.019), a reduced resting lung function (FEV1% of predicted 77 (67-84) vs. 96 (84-100); p < 0.001) and a pronounced anxiety trait at HADS (9.5 (3-11.7) vs. 4.0 (2.0-7.5); p = 0.023). In addition, SA patients showed a significantly higher reduction in inspiratory capacity from rest to peak (310 (160-520) vs. 110 (-65-325) ml; p = 0.031). We found no significant differences in mean daily step count or quality of life. CONCLUSIONS: Compared to MMA, SA patients present a reduced exercise capacity and a more pronounced anxiety trait, but not worse daily physical activity or quality of life. These aspects should be considered in the clinical management and research development of SA.

Long-term outcomes of combination biologic therapy in uncontrolled severe asthma: a case study.

INTRODUCTION: Treatment with biologics has significantly reduced the social and economic burden of severe asthma. However, some patients may still feature a suboptimal control of their symptoms while on therapy. In this subset of asthmatic patients, a benefit from a dual biologic therapy has sporadically been reported in literature. Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies. CASE STUDY: Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy. Omalizumab was started in 2008 with an initial remarkable clinical improvement. After nine years of biologic therapy, she reported a gradual worsening of her symptoms and exacerbations. Mepolizumab was then added in 2019. RESULTS: The addition of Mepolizumab resulted in a meaningful amelioration of her quality of life, asthma control, number of exacerbations and 6-minute-walking-distance at 3-year follow-up. The average Prednisone dosage was tapered from 25 mg to 20 mg daily. No adverse events were observed since the introduction of the second biologic. CONCLUSION: Our experience indicates that Mepolizumab may be beneficial and safe as an add-on biologic in a patient whose allergic and eosinophilic asthma remains uncontrolled despite treatment with an anti-IgE strategy. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes published so far are replicable on a larger scale.

Severity does not impact on exercise capacity in COVID-19 survivors.

BACKGROUND: current data on the impact of acute illness severity on exercise capacity and ventilatory efficiency of COVID-19 survivors, evaluated at cardiopulmonary exercise test (CPET), are limited. METHODS: in this post-hoc analysis of our previous observational, prospective, cohort study on mechanisms of exercise intolerance in COVID-19 survivors, we aimed at evaluating the impact of acute COVID-19 severity on exercise capacity, pulmonary function testing (PFT) and chest computed tomography (CT) outcomes. RESULTS: we enrolled 75 patients (18 with mild-to-moderate disease, 18 with severe disease, and 39 with critical disease). Mean (standard deviation - SD) follow-up time was 97 (26) days. Groups showed a similar PFT and CT residual involvement, featuring a mildly reduced exercise capacity with comparable mean (SD) values of peak oxygen consumption as percentage of predicted (83 (17) vs 82 (16) vs 84 (15), p = 0.895) among groups, as well as the median (interquartile range - IQR) alveolar-arterial gradient for O2 in mmHg at exercise peak (20 (15-28) vs 27 (18-31) vs 26 (21-21), p = 0.154), which was in the limit of normal. In addition, these patients featured a preserved mean ventilatory efficiency evaluated through the slope of the relation between ventilation and carbon dioxide output during exercise (27.1 (2.6) vs 29.8 (3.9) vs 28.3 (2.6), p = 0.028), without a clinically relevant difference. CONCLUSIONS: Disease severity does not impact on exercise capacity in COVID-19 survivors at 3 months after discharge, including a ventilatory response still in the limit of normal.

SARS-CoV-2-related ARDS in a maintenance hemodialysis patient: case report on tailored approach by daily hemodialysis, noninvasive ventilation, tocilizumab, anxiolytics, and point-of-care ultrasound.

Without rescue drugs approved, holistic approach by daily hemodialysis, noninvasive ventilation, anti-inflammatory medications, fluid assessment by bedside ultrasound, and anxiolytics improved outcomes of a maintenance hemodialysis patient affected by severe COVID-19.

Point-of-Care Lung Sonography: An Audit of 1150 Examinations.

OBJECTIVES: Point-of-care lung sonography has theoretical usefulness in numerous diseases; however clinical indications and the impact of this technique have not been fully investigated. We aimed to describe the current use of point-of-care lung sonography. METHODS: A 2-year prospective observational study was performed by pulmonologists in an Italian university hospital. Techniques, indications, consequences of lung sonography, and barriers to the examination were analyzed. RESULTS: A total of 1150 lung sonographic examinations were performed on 951 patients. The most common indications were diagnosis and follow-up of pleural effusion in 361 cases (31%), evaluation of lung consolidation (322 [28%]), acute heart failure (195 [17%]), guide to pleural procedures (117 [10%]), pneumothorax (54 [5%]) and acute exacerbations of chronic obstructive pulmonary disease (30 [3%]). The mean duration of the examination ± SD was 6 ± 4 minutes. The transducers most frequently used were convex (746 [65%]) and linear (161 [14%]), whereas in 205 examinations (18%), both transducers were used. According to the judgment of the caring clinician, 51% of the examinations were clinically relevant. CONCLUSIONS: Point-of-care lung sonography performed by pulmonologists is quick and feasible and could be widely used for different clinical indications with a potentially high clinical impact. The widespread use of this technique may have a relevant clinical impact in several indications.

Transbronchial needle aspiration in peripheral pulmonary lesions: a systematic review and meta-analysis.

Fluoroscopy-guided transbronchial needle aspiration (TBNA) has long been used in the diagnosis of peripheral pulmonary lesions (PPLs), although its diagnostic performance varies considerably.We conducted a systematic review and meta-analysis evaluating the accuracy of TBNA in the diagnosis of PPLs, comparing its diagnostic yield with transbronchial biopsy (TBB) and assessing the main predictors of a successful aspirate.In 18 studies, the overall TBNA yield was 0.53 (95% CI 0.44-0.61). TBNA showed a higher accuracy when directly compared to TBB (0.60 (95% CI 0.49-0.71) versus 0.45 (95% CI 0.37-0.54)). The subgroup analyses documented a higher TBNA yield when the computed tomography (CT) bronchus sign was present (0.70 (95% CI 0.63-0.77) versus 0.51 (95% CI 0.38-0.64)), when rapid on-site evaluation (ROSE) was performed (0.62 (95% CI 0.43-0.79) versus 0.51 (95% CI 0.42-0.60)), in the case of malignant lesions (0.55 (95% CI 0.44-0.66) versus 0.17 (95% CI 0.11-0.24)) and for lesions >3 cm (0.81 (95% CI 0.73-0.87) versus 0.55 (95% CI 0.47-0.63)).Conventional TBNA is a useful sampling technique for the diagnosis of PPL, with a higher diagnostic yield than TBB. The presence of CT bronchus sign, an underlying malignant process, lesion size >3 cm and ROSE employment are predictors of a higher yield.

Huge Tracheal Diverticulum in a Patient with Mounier-Kuhn Syndrome.

Tracheal diverticulum is a rare benign entity. Tracheobronchomegaly (TBM), also known as Mounier-Kuhn syndrome, is a rare disorder characterized by marked dilation of the trachea and main bronchi, associated with thinning or atrophy of the elastic tissue. Because of the weakened trachea and increased intraluminal pressure related to chronic cough, some patients may develop mucosal herniation leading to tracheal diverticulosis. We report the case of a patient with TBM with a huge tracheal diverticulum, diagnosed by bronchoscopy and computed tomography with three-dimensional reconstruction. to our knowledge this is the largest tracheal diameter described in a patient affected by this syndrome. LEARNING POINTS: Tracheal diverticulum is a rare condition that should be considered in the presence of bronchopulmonary disorders characterized by chronic cough and repeated bronchial infection, such as Mounier-Kuhn syndrome.The differential diagnosis of tracheal diverticulum includes laryngocele, pharyngocele, Zenker's diverticulum, apical lung hernia and lung bullae.Bronchoscopy and CT scans with three-dimensional reconstruction are useful tools for diagnosing this rare condition.