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 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.

scholarly journals Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
François Maltais ◽  
Leif Bjermer ◽  
Edward M. Kerwin ◽  
Paul W. Jones ◽  
Michael L. Watkins ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Inhaled Corticosteroids ◽  
Randomised Trial ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Short Term ◽  
Double Blind ◽  
Once Daily ◽  
Clinically Important Deterioration ◽  
Exacerbation Risk

Abstract Background Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids. Methods The 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to umeclidinium/vilanterol 62.5/25 μg once-daily, umeclidinium 62.5 μg once-daily or salmeterol 50 μg twice-daily. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions. Results Change from baseline in trough FEV1 at Week 24 was 66 mL (95% confidence interval [CI]: 43, 89) and 141 mL (95% CI: 118, 164) greater with umeclidinium/vilanterol versus umeclidinium and salmeterol, respectively (both p < 0.001). Umeclidinium/vilanterol demonstrated consistent improvements in Transition Dyspnoea Index versus both monotherapies at Week 24 (vs umeclidinium: 0.37 [95% CI: 0.06, 0.68], p = 0.018; vs salmeterol: 0.45 [95% CI: 0.15, 0.76], p = 0.004) and all other symptom measures at all time points. Regardless of the clinically important deterioration definition considered, umeclidinium/vilanterol significantly reduced the risk of a first clinically important deterioration compared with umeclidinium (by 16–25% [p < 0.01]) and salmeterol (by 26–41% [p < 0.001]). Safety profiles were similar between treatments. Conclusions Umeclidinium/vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimise therapy in this patient group.

scholarly journals Maintained therapeutic effect of revefenacin over 52 weeks in moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Sanjay Sethi ◽  
Brett Haumann ◽  
Srikanth Pendyala ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Health Outcomes ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Open Label ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Abstract Background Revefenacin is a long-acting muscarinic antagonist that was recently approved for the nebulized treatment of chronic obstructive pulmonary disease (COPD). Although shorter duration studies have documented the efficacy of revefenacin in COPD, longer-term efficacy has not been described. In a recent 52-week safety trial, revefenacin was well tolerated and had a favorable benefit-risk profile. Here we report exploratory efficacy and health outcomes in patients receiving revefenacin 175 μg or 88 μg daily during the 52-week trial. Methods In this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 175 μg or 88 μg in a double-blind manner, or open-label active control tiotropium. Results Over the 52-week treatment period, both doses of revefenacin, as well as tiotropium, elicited significant (all p < 0.0003) improvements from baseline in trough forced expiratory volume in 1 s (FEV1). The trough FEV1 profile (least squares mean change from baseline) for revefenacin 175 μg ranged from 52.3–124.3 mL and the trough FEV1 profile for tiotropium ranged from 79.7–112.8 mL. In subgroup comparisons, the effect of revefenacin on trough FEV1 was comparable in patients taking concomitant long-acting β-agonists, with or without inhaled corticosteroids, with patients who were not taking these medications. There were statistically significant (p < 0.05) improvements in all measured health status outcomes (evaluated using St. George’s Respiratory Questionnaire, COPD Assessment Test, Clinical COPD Questionnaire and Baseline and Transition Dyspnea Index) from 3 months onward, in all treatment arms. Conclusions Significant sustained improvements from baseline in trough FEV1 and respiratory health outcomes were demonstrated for 175-μg revefenacin over 52 weeks, further supporting its use as a once-daily bronchodilator for the nebulized treatment of patients with COPD. Trial registration NCT02518139; Registered 5 August 2015.

The infant and toddler with wheezing

2019 ◽  
Vol 40 (6) ◽  
pp. 393-395
Author(s):  
Nurcicek Padem ◽  
Rachel Glick Robison
Keyword(s):  
Young Children ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
Bacterial Colonization ◽  
High Dose ◽  
Predictive Index ◽  
Double Blind ◽  
Recurrent Wheezing ◽  
Young Infants ◽  
Tract Infections

Recurrent wheezing is common in young infants and toddlers, with 50% of all children having at least one wheezing episode in the first 6 years of life. Initial wheezing episodes in young children often are linked to respiratory infections due to viral pathogens, such as respiratory syncytial virus, human rhinovirus, human metapneumovirus, and influenza virus. Bacterial colonization of the neonatal airway also may be significant in the late development of recurrent wheeze and asthma. Wheezing in young children can be classified into specific phenotypes based on the onset and persistence of wheezing. Although some children will only wheeze transiently in early childhood, persistent wheezing is often classified as immunoglobulin E (IgE) associated and/or atopic or nonatopic. By using a modified asthma predictive index, future development of asthma can be interpreted, especially in high-risk populations. It is recommended to follow National Asthma Education and Prevention Program (NAEPP) guidelines for initiation of treatment; however, asthma management of young children often requires tailored regimens. Inhaled corticosteroids used as a daily controller medication have been shown to aid symptoms and exacerbation control; however, these do not change the natural course of the disease or progression to asthma. Although randomized double-blind studies in preschoolers investigated a role of macrolide antibiotics in early infection as well as high-dose inhaled corticosteroids during severe lower respiratory tract infections, more research is needed in this field to understand mechanisms of asthma development and optimal treatment in this young age group.

Airway responses to methacholine in asymptomatic nonatopic cigarette smokers

1987 ◽  
Vol 62 (5) ◽  
pp. 1888-1892 ◽  
Author(s):  
T. B. Casale ◽  
B. J. Rhodes ◽  
A. L. Donnelly ◽  
J. M. Weiler
Keyword(s):  
Pulmonary Function ◽  
Respiratory Infections ◽  
Allergic Diseases ◽  
Airway Disease ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Base Line ◽  
Young Smokers ◽  
Clinically Significant ◽  
Airway Responses

We prospectively performed methacholine bronchoprovocation challenges on 46 young smokers to examine the effects of cigarette smoking on airway responsiveness. The subjects, ages 18–35 yr, had no past or present history or physical examination findings of asthma or other lung diseases, rhinitis, allergic diseases, or respiratory infections; were skin test negative to 29 common aeroallergens; and had base-line pulmonary function values greater than 80% predicted. Sixteen of 46 (35%) subjects had a 20% or greater drop in forced expiratory volume in 1 s at a provocative methacholine concentration less than or equal to 25 mg/ml. The degree of methacholine responsiveness was not dependent upon base-line pulmonary function values or the amount of cigarettes consumed, and there was no association between the amount of cigarettes consumed and base-line pulmonary function values. These data suggest that many young asymptomatic nonatopic smokers have increased airway responsiveness to inhaled methacholine without clinically significant hyperreactive airway disease.

A case of immune-complex mediated glomerulonephritis associated with pembrolizumab

2021 ◽  
pp. 239936932110646
Author(s):  
Marco Bonilla ◽  
Vanesa Bijol ◽  
Antonio Gabriel De Leon Corona ◽  
Kevin M. Sullivan ◽  
Kenar D. Jhaveri
Keyword(s):  
Acute Kidney Injury ◽  
Immune Complex ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
High Dose ◽  
Dramatic Improvement ◽  
Pathologic Finding ◽  
Glomerular Injury ◽  
Metastatic Lung ◽  
Dose Prednisone

Introduction: Immune checkpoint inhibitors (ICI) are changing the way we treat cancer. However, these novel agents have various systemic adverse events that may preclude its use and cause poor patient outcomes. ICI-associated acute kidney injury is an emerging complication of this treatment. While tubulointerstitial disease is the most common pathologic finding of patients with ICI-associated AKI, there is sparse data in medical literature describing its association with glomerular disease. Case report: Here, we present a patient with metastatic lung adenocarcinoma who developed acute kidney injury and significant proteinuria after receiving pembrolizumab. The kidney biopsy revealed a membranoproliferative and diffuse segmental endocapillary proliferative pattern of glomerular injury. Management and outcome: Pembrolizumab was then held and high-dose prednisone was initiated, resulting in a rapid and dramatic improvement in kidney function and proteinuria. Discussion: We highlight a report of a patient diagnosed with immune-complex mediated glomerulonephritis associated with the use of pembrolizumab, who was successfully treated with drug withdrawal and corticosteroids.

Proof-of-concept evaluation of trough airway hyper-responsiveness following regular racemic or levosalbutamol in genotype-stratified steroid-treated persistent asthmatic patients

2013 ◽  
Vol 126 (1) ◽  
pp. 75-83 ◽  
Author(s):  
William J. Anderson ◽  
Philip M. Short ◽  
Peter A. Williamson ◽  
Ashley E. Morrison ◽  
Colin Palmer ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Proof Of Concept ◽  
Post Dose ◽  
Double Blind ◽  
Asthmatic Patients ◽  
On Demand ◽  
Concept Evaluation ◽  
Doubling Dilution

Asthmatic patients receiving ICSs (inhaled corticosteroids) may take frequent add-on therapy with salbutamol despite on-demand prescription. Frequent salbutamol use can be detrimental in asthma. The isomeric formulation of salbutamol and the B2ADR (β2 adrenoceptor) 16 genotype may also influence this phenomenon. We performed a randomized, double-blind, placebo-controlled, triple crossover, proof of concept trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol [200 μg q.i.d. (four times daily)], levosalbutamol (100 μg q.i.d.) or placebo on trough methacholine PC20 [provocative concentration causing 20% fall in FEV1 (forced expiratory volume in 1 s)] 6 h post-dose (the primary outcome) in 30 persistent asthmatic patients (15 who were Arg16 homozygous and 15 who were Gly16 homozygous) all receiving ICSs. There was no worsening of AHR (airway hyper-responsiveness) at trough to methacholine after 2 weeks regular exposure to either racemic (P=0.53) or levosalbutamol (P=0.84) compared with placebo, nor between genotypes–as dd (doubling dilution) difference in methacholine PC20 from placebo [salbutamol/Arg16=0.36 dd [95% CI (confidence interval), −0.43, 1.15]; salbutamol/Gly16=0.01 dd (95% CI, −0.47, 0.49); levosalbutamol/Arg16=−0.01 dd (95% CI, −0.89, 0.87); and levosalbutamol/Gly16=0.28 dd (95% CI, −0.22, 0.77)]. Both active treatments improved morning PEF (peak expiratory flow) in Gly16 (P=0.04 overall) but not Arg16 (P=0.50 overall) patients, whereas evening PEF improved in both Gly16 (P<0.001 overall) and Arg16 (P=0.006 overall) patients. In conclusion, the regular exposure to either racemic or levosalbutamol for 2 weeks added to ICSs did not cause worsening of AHR at trough compared with placebo; with no difference seen between B2ADR 16 genotypes.

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