scholarly journals Neutrophilic asthma: a complex phenotype of severe asthma

2020 ◽  
Vol 7 (1) ◽  
pp. 18-24
Author(s):  
Nightingale Syabbalo
Keyword(s):  
Inhaled Corticosteroids ◽  
Respiratory Infections ◽  
Airway Disease ◽  
Sleep Apnoea ◽  
High Dose ◽  
Interleukin 17 ◽  
Complex Phenotype ◽  
Obstructive Sleep ◽  
Chronic Airway Disease ◽  
High Doses

Asthma is a common chronic airway disease affecting about 334 million people worldwide, and an estimated 7 million children globally. Approximately 10% of patients with asthma have severe refractory disease, which is difficult to control on high doses of inhaled corticosteroids and other modifiers. Among these, are patients with severe neutrophilic asthma. Neutrophilic asthma is a phenotype of asthma that is very severe and persistent, with frequent exacerbations, and characterized by fixed airway obstruction. It is associated with comorbidities such as respiratory infections, obesity, gastroeosophageal reflux disease, and obstructive sleep apnoea. Immunopathologically, it is characterized by the presence of high levels of neutrophils in the lungs and airways. Neutrophils and the interleukin-17 family of cytokines play a pivotal role in the pathogenesis of severe neutrophilic asthma. Most patients with the disease do not achieve control with high dose inhaled corticosteroids, and probably to novel IgE, interleukin and interleukin monoclonal antibodies.

Bronchiolitis als mögliche unerwünschte Wirkung von Immuncheckpoint-Inhibitoren

2020 ◽  
Vol 8 (3) ◽  
pp. 152-153
Author(s):  
Nicolas Carlos Kahn
Keyword(s):  
Inhaled Corticosteroids ◽  
Respiratory Infections ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Airway Disease ◽  
Forced Expiratory Volume ◽  
Functional Improvement ◽  
High Dose ◽  
Double Blind ◽  
Dose Prednisone

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

scholarly journals Comparative risks of chronic inhaled corticosteroids and macrolides for bronchiectasis

2019 ◽  
Vol 54 (1) ◽  
pp. 1801896 ◽  
Author(s):  
Emily Henkle ◽  
Jeffrey R. Curtis ◽  
Lang Chen ◽  
Benjamin Chan ◽  
Timothy R. Aksamit ◽  
...  
Keyword(s):  
Acute Exacerbation ◽  
Respiratory Infection ◽  
Cox Regression ◽  
Inhaled Corticosteroids ◽  
Respiratory Infections ◽  
Airway Disease ◽  
International Classification Of Diseases ◽  
Increased Risk ◽  
Chronic Airway Disease ◽  
Mean Differences

IntroductionNon-cystic fibrosis (CF) bronchiectasis (“bronchiectasis”) is a chronic airway disease for which little data exist to inform treatment decisions. We sought to compare the risks of respiratory infections in chronic users of inhaled corticosteroids (ICSs) versus macrolide monotherapy.MethodsWe identified a cohort of US Medicare enrollees with a bronchiectasis diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 494.0 or 494.1) between 2006 and 2014, excluding CF. We defined chronic new use as the first ≥28-day prescription of ICS therapy or macrolide monotherapy. We compared the characteristics of the exposure cohorts using standardised mean differences (SMDs) and computed a propensity score (PS) to account for treatment differences. The risks of acute exacerbation, hospitalised respiratory infection, all-cause hospitalisation and mortality were compared using PS decile-adjusted Cox regression models.ResultsWe identified 83 589 new users of ICSs and 6500 new users of macrolides from 285 043 included Medicare enrollees with bronchiectasis. The crude incidence of hospitalised respiratory infection was 12.6 (ICS therapy) and 10.3 (macrolide monotherapy) per 100 patient-years. The PS-adjusted HRs comparing ICS with macrolide new users were 1.39 (95% CI 1.23–1.57) for hospitalised respiratory infection, 1.56 (95% 1.49–1.64) for acute exacerbation and 1.09 (95% 0.95–1.25) for mortality.InterpretationAmong patients with bronchiectasis, the use of ICSs was associated with an increased risk of hospitalised respiratory infections compared with macrolide monotherapy.

scholarly journals Severe Neutrophilic Asthma: Pathogenesis and Treatment

2022 ◽  
Vol 3 (1) ◽  
pp. 01-13
Author(s):  
Nightingale Syabbalo
Keyword(s):  
Cell Injury ◽  
Inhaled Corticosteroids ◽  
Fungal Infections ◽  
Unmet Need ◽  
Airway Disease ◽  
Airway Epithelial Cells ◽  
High Dose ◽  
Interleukin 17 ◽  
Airway Epithelial ◽  
Eosinophilic Asthma

Asthma is a common chronic airway disease affecting about 358 million people worldwide, and an estimated 7 million children globally. Approximately 10% of patients with asthma have severe refractory disease, which is difficult to control on high doses of inhaled corticosteroids and other modifiers. Among these, are patients with severe neutrophilic asthma. Neutrophilic asthma is a severe phenotype of asthma, characterized by frequent exacerbations, persistent airway obstruction, and poor lung function. Immunopathologically, it is characterized by the presence of high levels of neutrophils in the airways and lungs. Interleukin-17 produced by Th17 cells, plays a key role in the pathogenesis of neutrophilic asthma by expressing the secretion of chemoattractant cytokines and chemokines for the recruitment, and activation of neutrophils. Interleukin-8 is a powerful chemoattractant and activator of neutrophils. Activated neutrophils produce an oxidative burst, releasing multiple reactive oxygen species, proteinases, cytokines, which cause airway epithelial cell injury, inflammation, airway hyperresponsiveness, and remodeling. Furthermore, exasperated neutrophils due to viral, bacterial or fungal infections, and chemical irritants can release extracellular nucleic acids (DNA), designated as NETs (neutrophil extracellular traps), which are more toxic to the airway epithelial cells, and orchestrate airway inflammation, and release alarmin cytokines. Dysregulated NETs formation is associated with severe asthma. Most patients with neutrophilic asthma are unresponsive to the standard of care, including high dose inhaled corticosteroids, and to targeted biologics, such as mepolizumab, and dupilumab, which are very effective in treating eosinophilic asthma. There is unmet need to explore for novel biologics for the treatment of neutrophilic asthma, and in refining therapies, such as bronchial thermoplasty.

scholarly journals Factors associated with outcomes of septic shock patients receiving high dose noradrenaline according to three primary infection sites

2019 ◽  
Vol 48 (2) ◽  
pp. 030006051987454
Author(s):  
Kang-song Wu ◽  
Dan-yan Gu ◽  
Ting-ting Wang ◽  
Bu-wen Yu ◽  
Kong-han Pan ◽  
...  
Keyword(s):  
Septic Shock ◽  
Primary Infection ◽  
Medical Information ◽  
Respiratory Infections ◽  
High Dose ◽  
Do Not Resuscitate ◽  
Factors Associated ◽  
Risk Of Death ◽  
Urinary Infections ◽  
High Doses

Objective To identify factors associated with outcome of septic shock patients receiving high dose noradrenaline according to three primary infection sites. Methods This retrospective study was based on data from a publicly available ICU database (Medical Information Mart for Intensive Care [MIMIC] III. Septic shock patients receiving high dose (≥1 μg/kg per min) noradrenaline and ≥18 years were identified and their characteristics and outcomes were compared according to three primary infection sites (abdominal, respiratory and urinary tract). Results 154 septic shock patients who received high doses of noradrenaline were identified; (89 [58%] had a respiratory infection, 41 [27%] an abdominal infection and 24 [16%] a urinary infection). There were no differences among the three infection groups in duration/maximum dosage of noradrenaline, length of stay in the ICU/hospital, do not resuscitate (DNR) rates, hypertension and adequate antimicrobial therapy. Patients with urinary infections had a lower risk of death at 28-days compared with those with abdominal or respiratory infections. Conclusions The prognosis for septic shock patients receiving high dose noradrenaline is poor. Patients with abdominal or respiratory infections are at higher risk of death compared with those with urinary infections.

scholarly journals Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea

2020 ◽  
Author(s):  
Joshua M. Bock ◽  
Brady E. Hanson ◽  
Thomas F. Asama ◽  
Andrew J. Feider ◽  
Satoshi Hanada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Ventilatory Response ◽  
High Dose ◽  
Inorganic Nitrate ◽  
Obstructive Sleep ◽  
Chemoreflex Sensitivity ◽  
Nitrate Supplementation ◽  
High Doses ◽  
Peripheral Chemoreflex

Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53±10years, 29.2±5.8kg/m2, apnea-hypopnea index=17.8±8.1, 43%F) completed three visits. Resting brachial blood pressure, as well as cardiopulmonary responses to inspiratory hypoxia, were measured before, and two hours after, acute inorganic nitrate supplementation (~0.10mmol [placebo], 4.03mmol [low-dose], and 8.06mmol [high-dose]). Placebo did not increase either plasma [nitrate] (30±52 to 52±23μM, P=0.26) or [nitrite] (266±153 to 277±164nM, P=0.21); however, both increased following low-(29±17 to 175±42μM, 220±137 to 514±352nM) and high-doses (26±11 to 292±90μM, 248±155 to 738±427nM, respectively, P<0.01 for all). Following placebo, systolic blood pressure increased (120±9 to128±10mmHg, P<0.05) whereas no changes were observed following low-(121±11 to 123±8mmHg, P=0.19) or high-dose (124±13 to 124±9mmHg, P=0.96). The peak ventilatory response to hypoxia increased following placebo (3.1±1.2 to 4.4±2.6L/min, P<0.01) but not low-(4.4±2.4 to 5.4±3.4L/min, P=0.11) or high-doses (4.3±2.3 to 4.8±2.7L/min, P=0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P=0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.

scholarly journals Detecting COVID-19 and other respiratory infections in obstructive sleep apnoea patients through CPAP device telemonitoring

2021 ◽  
Vol 7 ◽  
pp. 205520762110029
Author(s):  
Jean-Louis Pépin ◽  
Sébastien Bailly ◽  
Jean-Christian Borel ◽  
Sophie Logerot ◽  
Marc Sapène ◽  
...  
Keyword(s):  
Continuous Positive Airway Pressure ◽  
Obstructive Sleep Apnoea ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Respiratory Infections ◽  
Sleep Apnoea ◽  
First Line Therapy ◽  
Obstructive Sleep ◽  
Device Use ◽  
Spread Of Infection

Objective The earliest possible detection of individuals with COVID-19 has been essential to curb the spread of infection. Existing digital tools have been scaled up to address this issue. Every night telemonitoring data on continuous positive airway pressure (CPAP) device use, the first-line therapy for obstructive sleep apnoea (OSA), is collected worldwide. We asked whether the changes in CPAP adherence patterns of might constitute an alert for COVID-19. Methods We analysed preliminary results of telemonitoring data, recorded between February 1 and April 30, 2020, on OSA patients followed by our sleep clinics and diagnosed with COVID-19. Results CPAP telemonitoring data from the first 19 patients diagnosed with COVID-19 showed a clear decrease or halt in adherence in the 20 days immediately preceding COVID-19 diagnosis compared to an earlier period (p < 0.01). Conclusion Patterns of continuous positive airway pressure device use by obstructive sleep apnoea patients collected through telemonitoring can indicate the onset of COVID-19 symptoms. Existing telemonitoring platforms could be immediately used to screen for COVID-19, and for other respiratory infections, in this large at-risk population.

scholarly journals Bronchial Thermoplasty in the Treatment of Severe Asthma

2020 ◽  
pp. 1-9
Author(s):  
Nightingale Syabbalo ◽  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Airway Disease ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
High Dose ◽  
Eosinophilic Asthma ◽  
Bronchial Thermoplasty ◽  
Long Acting ◽  
Refractory Asthma

Asthma is a chronic inflammatory airway disease with several distinct phenotypes, characterized by different immunopathological pathways, clinical presentation, severity of the disease, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma. Approximately 3.6-10% of patients with asthma have severe refractory disease, which is unresponsive to high dose inhaled corticosteroids (ICS), and long-acting β2-agonists (LABA). Most patients with eosinophilic asthma are responsive to corticosteroids, and interleukintargeted biologics, whereas, patients from other phenotypes, such as neutrophillic and paucigranullocytic asthma are resistant to treatment with ICS and biotherapeutics. The hallmark of severe refractory asthma is airway hyperresponsiveness, and remodeling. Histopathologically, patients with severe asthma have airway smooth muscle (ASM) hyperplasia and hypertrophy; subepithelial basement membrane thickening and fibrosis; all which contribute to fixed airflow limitation. Severe refractory asthma is very difficult to treat pharmacologically. It requires innovative therapies, such as bronchial thermoplasty which reduces the hypertrophied ASM mass and relieves the AHR, and broncoconstriction. Bronchial thermoplasty has been shown to improve asthma control, reduce severe exacerbations, hospitalizations, emergency room visits, and improve the quality of life, which persist up to 5 years following the procedure

scholarly journals Overuse of Oral Corticosteroids, Underuse of Inhaled Corticosteroids, and Implications for Biologic Therapy in Asthma

Respiration ◽  
2021 ◽  
pp. 1-6
Author(s):  
Katrien Eger ◽  
Marijke Amelink ◽  
Simone Hashimoto ◽  
Pieter-Paul Hekking ◽  
Cristina Longo ◽  
...  
Keyword(s):  
Biologic Therapy ◽  
Inhaled Corticosteroids ◽  
Inhalation Technique ◽  
High Dose ◽  
Inhaler Technique ◽  
Biologic Treatment ◽  
Asthma Patients ◽  
Oral Corticosteroids ◽  
High Doses ◽  
Steroid Sparing

<b><i>Background:</i></b> Asthma patients using high cumulative doses of oral corticosteroids (OCSs) are at risk of serious adverse events and are increasingly being treated with steroid-sparing asthma biologics. However, it is unknown whether prescribing these expensive biologics is always justified. <b><i>Objectives:</i></b> This study aimed to (1) assess the prevalence of asthma patients using high cumulative doses of OCSs, (2) explore the role of suboptimal inhaler therapy, and (3) estimate the proportion of patients to whom asthma biologics might be prescribed unnecessarily. <b><i>Methods:</i></b> All adults (<i>n</i> = 5,002) with at least 1 prescription of high-dose inhaled corticosteroids (≥500–1,000 mcg/day fluticasone-equivalent) and/or OCSs (GINA step 4–5) in 2010 were selected from a pharmacy database including 500,500 Dutch inhabitants, and sent questionnaires. Of 2,312 patients who returned questionnaires, 929 had asthma. We calculated the annual cumulative OCS dose and prescription fillings and checked inhaler technique in a sample of 60 patients. Patients estimated to have good adherence and inhaler proficiency who still required high doses of OCSs (≥420 mg/year) were considered candidates for initiating biologic treatment. <b><i>Results:</i></b> 29.5% of asthma patients on GINA 4–5 therapy used high doses of OCSs, of which 78.1% were likely to have poor therapy adherence or inadequate inhaler technique. Only 21.9% were considered definitive candidates for biologic therapy. <b><i>Conclusion:</i></b> High OCS use in Dutch GINA 4–5 asthma patients was common. However, in 4 out of 5 patients adherence to inhaled corticosteroid therapy and/or inhalation technique was considered suboptimal. Since optimizing inhaler therapy may reduce the need for OCSs, this should be mandatory before prescribing expensive steroid-sparing drugs.

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