Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy

AbstractCanakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1β and has been approved by the US Food and Drug Administration for treating different types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1β by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1β-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1β-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1β neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1β-downstream signaling and IL-1β-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future.

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Quality Of Life In Patients Taking Guaifenesin And Pseudoephedrine In An Extended-release Bi-layer Tablet As First-line Symptomatic Therapy For Acute Upper Respiratory Tract Infections (URI)

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2010.12.801 ◽

2011 ◽

Vol 127 (2) ◽

pp. AB201-AB201 ◽

Cited By ~ 1

Author(s):

H.G. Mariano Jr. ◽

G. Solomon ◽

E.C. Steward ◽

H.H. Albrecht

Keyword(s):

Quality Of Life ◽

Respiratory Tract Infections ◽

Extended Release ◽

Upper Respiratory Tract Infections ◽

Symptomatic Therapy ◽

Upper Respiratory Tract ◽

First Line ◽

Upper Respiratory ◽

Tract Infections

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Nasal disease and quality of life in athletes

The Journal of Laryngology & Otology ◽

10.1017/s0022215118001408 ◽

2018 ◽

Vol 132 (9) ◽

pp. 812-815

Author(s):

A C Walker ◽

P Surda ◽

M Rossiter ◽

S A Little

Keyword(s):

Quality Of Life ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Upper Respiratory Tract Infections ◽

Upper Respiratory Tract ◽

Nasal Symptoms ◽

Nasal Disease ◽

Upper Respiratory ◽

Tract Infections

AbstractObjectivesNasal disease imposes a significant disease burden upon the individual in the general population, but is relatively under studied in athletes. This study sought to define the frequency of nasal symptoms in the active population, and to quantify the impact of these symptoms on quality of life and on the frequency of upper respiratory tract infections.ResultsA total of 296 participants completed the study (246 athletes and 50 sedentary controls). Nasal symptoms were significantly more frequent in the active group than in the sedentary controls (70 per cent vs 52 per cent). Upper respiratory tract infections were significantly more common in athletes with regular nasal symptoms than in athletes without nasal symptoms. Quality-of-life scores, as measured by the 22-item Sino-Nasal Outcome Test, were significantly worse in athletes with regular nasal symptoms.ConclusionThis study suggests that regular exercise is associated with a significant increase in the prevalence of troubling nasal symptoms, and nasal symptoms in athletes are associated with increased susceptibility to upper respiratory tract infections. Quality of life was negatively affected, confirming the importance of nasal health to athlete welfare.

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Quality of life in patients with smell loss due to upper respiratory tract infections

American Journal of Otolaryngology ◽

10.1016/j.amjoto.2010.11.002 ◽

2011 ◽

Vol 32 (6) ◽

pp. 504-510 ◽

Cited By ~ 11

Author(s):

Adolfo Toledano ◽

Gil Rodríguez ◽

Ana María Martín ◽

Tomás Onrubia ◽

Néstor Galindo

Keyword(s):

Quality Of Life ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Upper Respiratory Tract Infections ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Tract Infections ◽

Smell Loss

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A case-control study of medical, psychological and socio-economic factors influencing the severity of chronic rhinosinusitis

Rhinology Journal ◽

10.4193/rhino15.272 ◽

2016 ◽

Vol 54 (2) ◽

pp. 134-140

Author(s):

Carl Philpott ◽

Sally Erskine ◽

Claire Hopkins ◽

Emma Coombes ◽

Naveed Kara ◽

...

Keyword(s):

Quality Of Life ◽

Chronic Rhinosinusitis ◽

Final Analysis ◽

Psychiatric Disease ◽

Economic Factors ◽

Upper Respiratory Tract ◽

Tract Infections ◽

Snot 22 ◽

Socio Economic Factors

Background: Chronic rhinosinusitis (CRS) is a common and debilitating disorder. Little is known about the epidemiology of this disease. The aims of the study were to identify differences in socio-economic variables and quality of life between patients with chronic rhinosinusitis and healthy controls, to identify any significant associations between CRS and other medical co-morbidities, psychiatric disease or environmental exposure and to explore the experience of CRS from the perspective of CRS sufferers. Methods: Participants were recruited from ENT clinics from 30 centres across the UK. They completed a study-specific questionnaire considering environmental, medical and socio-economic factors, and SF-36 and SNOT-22 scores. All participants with CRS were diagnosed by a clinician and categorised as having CRS (with polyposis, without polyposis or allergic fungal rhinosinusitis (AFRS)). Controls included family and friends of those attending ENT outpatient clinics and hospital staff who had no diagnosis of nose or sinus problems and had not been admitted to hospital in the previous 12 months. Results: A total of 1470 study participants (1249 patients and 221 controls) were included in the final analysis. Highly significant differences were seen in generic and disease-specific quality of life scores between CRS sufferers and controls; mean SNOT-22 score 45.0 for CRS compared with 12.1 amongst controls. There were no clear differences in socioeconomic variables including social class, index of multiple deprivation and educational attainment between cases and controls. Common comorbidities with a clear association included respiratory and psychiatric disorders, with a higher frequency of reported upper respiratory tract infections. Conclusions: CRS is associated with significant impairment in quality of life and with certain medical co-morbidities. In contrast to other common ENT disorders, no socioeconomic differences were found between patients and controls in this study.

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Health-related quality of life of adults with upper respiratory tract infections

Journal of General Internal Medicine ◽

10.1046/j.1525-1497.2003.21246.x ◽

2003 ◽

Vol 18 (10) ◽

pp. 802-807 ◽

Cited By ~ 24

Author(s):

Jeffrey A. Linder ◽

Daniel E. Singer

Keyword(s):

Quality Of Life ◽

Respiratory Tract Infections ◽

Upper Respiratory Tract Infections ◽

Upper Respiratory Tract ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

Upper Respiratory ◽

Tract Infections

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Nagelpsoriasis: Anti-IL17-Therapie ist erfolgversprechend

Karger Kompass Dermatologie ◽

10.1159/000509299 ◽

2020 ◽

Vol 8 (3) ◽

pp. 111-113

Author(s):

Sandra Philipp

Keyword(s):

Quality Of Life ◽

Severity Index ◽

Primary Objective ◽

Controlled Study ◽

Upper Respiratory Tract ◽

Double Blind ◽

Nail Psoriasis ◽

Patient Questionnaires ◽

Tract Infections

Background: Nail psoriasis is associated with functional impairment, pain and reduced quality of life. Objectives: To demonstrate the superiority of secukinumab over placebo in clearing nail psoriasis as assessed by the Nail Psoriasis Severity Index (NAPSI) at week 16 and over time up to week 132. Presented here is the week 32 interim analysis. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) patient questionnaires. Methods: TRANSFIGURE is a double-blind, randomized, placebo-controlled study in patients with moderate-to-severe plaque and nail psoriasis. Results: The primary objective of this study was met: both doses of secukinumab were superior to placebo at week 16 (NAPSI improvements of -45,3%, -37,9% and -10,8% for secukinumab 300 mg and 150 mg and placebo, respectively, P<0,001). Significant improvements were seen in patients’ quality of life: the NAPPA-Quality of Life total score median decreases at week 16 were 60,9%, 49,9% and 15,8% for secukinumab 300 mg and 150 mg and placebo, respectively (P < 0_001). Improvement in nail psoriasis continued to week 32: NAPSI percentage change reached -63,2% and -52,6% for secukinumab 300 mg and 150 mg, respectively. Skin clearance measured by ≥90% improvement in Psoriasis. Area and Severity Index was significant (rates of 72,5%, 54,0% and 1,7% for secukinumab 300mg and 150mg and placebo at week 16, respectively, P<0,001) and was sustained to week 32. The most common adverse events were nasopharyngitis, headache and upper respiratory tract infections. Conclusion: Secukinumab demonstrated significant and clinically meaningful efficacy and quality-of-life improvements for patients with nail psoriasis up to week 32.

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Gangguan Fungsi Penghidu dan Pemeriksaannya

Jurnal Kesehatan Andalas ◽

10.25077/jka.v3i1.16 ◽

2014 ◽

Vol 3 (1) ◽

Author(s):

Effy Huriyati ◽

Tuti Nelvia

Keyword(s):

Quality Of Life ◽

Respiratory Tract Infections ◽

Olfactory Function ◽

Upper Respiratory Tract Infections ◽

Upper Respiratory Tract ◽

Conduction Disturbances ◽

Olfactory Disorder ◽

Upper Respiratory ◽

Tract Infections

AbstrakLatar belakang: Fungsi penghidu pada manusia memegang peranan penting. Gangguan penghidu dapat mempengaruhi keselamatan dan kualitas hidup seseorang. Tujuan: Untuk mengetahui jenis gangguan penghidu, penyebab gangguan penghidu, dan pemeriksaannya. Tinjauan Pustaka: Gangguan penghidu dapat berupa anosmia yaitu hilangnya kemampuan penghidu, atau hiposmia yaitu berkurangnya kemampuan penghidu. Gangguan penghidu disebabkan gangguan konduksi, gangguan sensoria dan gangguan neural. Penyakit tersering penyebab gangguan penghidu yaitu rinosinusitis kronis, rinitis alergi, infeksi saluran nafas atas dan trauma kepala. Ada beberapa modalitas pemeriksaan kemosensoris fungsi penghidu diantaranya Tes “Sniffin sticks”. Dengan tes „Sniffin sticks” dapat diketahui ambang penghidu, diskriminasi penghidu dan identifikasi penghidu seseorang. Kesimpulan: Gangguan penghidu memerlukan perhatian khusus. Diantara beberapa modalitas pemeriksaan kemosensoris penghidu, tes “Sniffin sticks” mempunyai beberapa kelebihan.Kata kunci: Gangguan penghidu, anosmia, hiposmia, tes “Sniffin sticks”.AbstractBackground: Olfactory function in humans plays an important role. Olfactory disorders can affect the safety and quality of life. Objective: To determine the type of olfactory disorder, the causes of olfactory disorders, and the examination. Literature Review: Olfactory disorder can be not smell anything or anosmia, and reduced of smell or hyposmia. Olfactory disorders caused by conduction disturbances, neural disturbances and sensoris disturbances. Disease that often causes disturbances of olfactory function is, chronic rhinosinusitis, allergic rhinitis, upper respiratory tract infections and head trauma. There are several modalities to examine chemosensoris smelling function, one of them is “Sniffin sticks” test. This test can examine threshold, discrimination, and identification of smelling. Conclusions: Impaired smelling require special attention. Between some modalities to examine chemosensors smelling function, “Sniffin sticks” test has several advantages.Keywords: Olfactory disorders, anosmia, hyposmia, “Sniffin sticks” test.

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Advances in the Management of Neurogenic Detrusor Overactivity in Multiple Sclerosis

International Journal of MS Care ◽

10.7224/1537-2073.2012-031 ◽

2013 ◽

Vol 15 (2) ◽

pp. 66-72 ◽

Cited By ~ 10

Author(s):

Gael J. Yonnet ◽

Anette S. Fjeldstad ◽

Noel G. Carlson ◽

John W. Rose

Keyword(s):

Quality Of Life ◽

Multiple Sclerosis ◽

Botulinum Toxin ◽

Urinary Tract ◽

Detrusor Overactivity ◽

Anticholinergic Drugs ◽

Neurogenic Detrusor Overactivity ◽

Botulinum Toxin Therapy ◽

Tract Infections

Bladder dysfunction in multiple sclerosis (MS) can be socially disabling, have negative psychological and economic consequences, and impair patients' quality of life. Knowledge of the functional anatomy and physiology of the urinary tract is essential to understand the symptoms associated with central nervous system lesions and the pharmacotherapies used to treat them. Treatments for neurogenic detrusor overactivity (NDO) have consisted mainly of administration of anticholinergic drugs, which have been shown to provide suboptimal clinical benefits and be poorly tolerated. The US Food and Drug Administration (FDA) approval of intravesicular botulinum toxin therapy provides a second-line option for MS patients with NDO not responsive to anticholinergic drugs. We performed a review of key literature pertaining to the intravesicular application of botulinum toxin. In the management of NDO, administration of intravesicular botulinum toxin using clean intermittent catheterization decreases the incidence of urinary tract infections, promotes urinary continence, and improves quality of life for 9 months after a single injection; moreover, those benefits are maintained with repeated injections over time.

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Quality of life in allergic rhinitis

Therapeutic Advances in Respiratory Disease ◽

10.1177/1753465811424425 ◽

2011 ◽

Vol 6 (1) ◽

pp. 25-39 ◽

Cited By ~ 34

Author(s):

Tunis Ozdoganoglu ◽

Murat Songu ◽

Hasan Mete Inancli

Keyword(s):

Quality Of Life ◽

Allergic Rhinitis ◽

School Performance ◽

Work Performance ◽

Upper Respiratory Tract ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

The Impact

Allergic rhinitis is a global health problem that causes major illness and disability worldwide. Although nasal and nonnasal symptoms are directly attributable to inflammation in the upper respiratory tract, individuals also experience generalized symptoms that include fatigue, mood changes, depression, anxiety and impairments of work and school performance, and cognitive function. Health-related quality of life focuses on patients’ perceptions of their disease and measures impairments that have a significant impact on the patient. The burden of disease, as the patient perceives it, forms the basic motivation to seek medical aid or to undergo therapy. Adherence to therapy requires changes in health, perceived by patients as relevant and outweighing eventual disadvantages of intervention. Because so many factors are involved in health-related quality of life, there are multiple ways in which it can be measured. A variety of validated and standardized questionnaires have been developed including assessments of school performance, work performance, productivity, and other parameters that quantify the impact of allergic rhinitis and its treatment on quality of life. The aim of this review is to highlight the impact of allergic rhinitis on the quality of life and to analyze the most commonly used health-related quality of life instruments.

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