
Role of IL-5R Signaling in Non-eosinophil Upper Airway Cells in CRSwNP
Nasal PolypsAspirin-exacerbated Respiratory DiseaseThe overarching hypothesis of this proposal is that IL-5 acts on multiple sinus tissue cell types, including plasma cells and epithelial cells, to promote immune dysregulation, and that inhibition of IL-5 affects several relevant effector pathways that lead to clinical benefit.

Mechanisms of Benefit of IL4RA Inhibition in Aspirin-Exacerbated Respiratory Disease
Nasal PolypsAsthma3 moreThe overall aim of the study is to determine the clinical efficacy and mechanisms of action of anti-IL-4a (dupilumab) as treatment for patients with Aspirin-Exacerbated Respiratory Disease (AERD).

Digital App for Telerehabilitation in Respiratory Diseases
Respiratory DiseaseAsthma5 moreThe purpose of this study is to evaluate the feasibility and the mid-term effects of a pulmonary rehabilitation intervention, delivered by digital App, on quality of life of patients affected by respiratory diseases. The App will include a monitored exercise training program based on most recent cardiopulmonary rehabilitation guidelines, including alerts, reminders and educational contents as well as chat and online visits with healthcare professionals to improve patient engagement.

Azithromycin and Oesophageal Function in Respiratory Disease
CoughAsthma2 moreSymptoms such as cough, wheeze, and breathlessness are among the most common reasons for general practitioner or emergency department visits in the UK. Such symptoms have a profound impact on patients' ability to live a fulfilled life, often rendering people unable to work and socialise. Azithromycin (a type of antibiotic) improves symptoms and reduces flare-ups of diseases such as asthma and chronic obstructive pulmonary disease (COPD). The reason why it works is unclear. Many people believe that it either decreases the number of bacteria in the lungs or reduces inflammation in the lungs and the upper airways. Neither theory is proven. Another possible mechanism that has been much less studied is that Azithromycin encourages the body to move food and fluid through the gut more quickly, thus preventing reflux and aspiration of small food particles and stomach acid. It has been shown that lung damage can occur when gut contents enter the airways, which may contribute chronic lung disease patients' symptoms In this study the investigators will test the effect of azithromycin on the gut in patients with chronic lung diseases. The investigators will measure the strength of a patients swallow by measuring the pressures in their gullet, using high-resolution oesophageal manometry (HROM), before and after treatment, in people being started on azithromycin as part of their routine care. The investigators will also measure the effect that azithromycin has on their symptoms and observe whether there is a relationship between the strength of their swallow and their symptoms. At the end of this study, the investigators hope to better understand the way in which azithromycin helps to improve the symptoms of patients with chronic lung diseases. The investigators also hope to open the door to investigate the effect of other drugs that improve gut function in patients with chronic lung diseases.

Spinal Cord Stimulation for Respiratory Rehabilitation in Patients With Chronic Spinal Cord Injury...
Spinal Cord InjuriesRespiration DisordersRespiratory complications are among the leading causes of death in patients with chronic spinal cord injury (SCI). Our previous work showed that pulmonary function can be improved by using our original respiratory training method. However, the effectiveness of this intervention is limited due to the disruption of brain-spinal connections and consequently lowered spinal cord activity below the injury level. Our recent studies showed that electrical stimulation of the spinal cord below the level of injury leads to increased ventilation which indicates activation of the spinal cord structures related to respiration. These findings indicate that spinal cord stimulation can be a promising therapeutic additive to the treatment. The goal of this study is to justify the establishment of a new direction in rehabilitation for patients with SCI by using a non-invasive spinal cord stimulation in combination with respiratory training. Our aims are: 1) to evaluate the effects of such stimulation applied to the injured spinal cord on pulmonary function and respiratory muscle activity, and 2) to evaluate the effectiveness and therapeutic mechanisms of the spinal cord stimulation combined with respiratory training. Thirty-six individuals with chronic SCI will be recruited and assigned to three groups to receive respiratory training or spinal cord stimulation alone or a combination of them. All participants will be tested before and after cycles of experimental procedures with/or without stimulation. Our hypotheses will be confirmed if the respiratory training combined with spinal cord stimulation results in the most enhanced positive effects.

Cohort for Research and Innovation in Chronic Inflammatory Respiratory Diseases
Chronic Inflammatory Pulmonary DiseasesChronic inflammatory pulmonary diseases including chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), bronchiectasis, and cystic fibrosis (CF) are characterized by lung inflammation and remodelling. Clinical, functional, microbiological, biological, pathological and prognosis features are highly variable and heterogeneous. A precise phenotyping is a key-element to better understanding the pathophysiology of these chronic inflammatory diseases and to develop innovative treatment strategies. The objectives of this prospective study is to analyze the clinical, demographic, biological, morphological, pathological, and microbiological characteristics in a cohort of patients diagnosed with COPD, ILD, bronchiectasis, and CF. The associations between clinical, demographic, biological, morphological, pathological, and microbiological features will be assessed. The Cohort for Research and Innovation in Chronic Inflammatory Respiratory Diseases (the RINNOPARI Project: Recherche et Innovation en Pathologie Respiratoire Inflammatoire) is a monocentric study conducted at the University Hospital of Reims, France. Adult patients (>18 year-old) followed at the University Hospital of Reims and diagnosed with COPD, ILD, bronchiectasis, or CF will be considered for inclusion. Patients will sign an informed consent for inclusion. Exclusion criteria include "subjects protected by the law" as required by the French authorities. Control patients with no respiratory diseases after clinical and pulmonary function tests assessment will be also included. The expected number of patients included is 225 (COPD, n=100; CF, n=25; bronchiectasis, n=25; ILD, n=25; controls, n=50). Inclusion will be conducted for 36 months from September 2016 (9/30/2016) to September 2019 (9/30/2019). For all COPD, ILD, bronchiectasis, and CF patients included, data will be registered at inclusion, and at follow-up visits for 10 years. Patients will be followed-up as usual care with no specific therapeutic intervention. For control patients, data will be registered at inclusion with no follow-up. Data will be registered in a centralized anonymized database. The characteristics of the patients will be described as mean and standard deviation for quantitative data and as number and percentages for qualitative data. Comparisons and associations between groups and variables will be analyzed by Student, Wilcoxon, Chi2, Fischer exact, and Spearman tests as applicable. A p<0.05 will be considered as significant. This study should help to better characterize clinical, demographic, biological, morphological, pathological, and microbiological characteristics and phenotypes in chronic inflammatory respiratory diseases.

NAC for Attenuation of COVID-19 Symptomatology
Covid19COVID-19 Pneumonia6 moreThe objective of this study is to determine whether oral NAC is effective at attenuating COVID-19 disease symptom severity and duration of symptoms.

Daily Vitamin D for Sickle-cell Respiratory Complications
Sickle Cell DiseaseAnemia13 moreThis study aims to answer the question whether daily oral vitamin D supplementation can reduce the risk of respiratory or lung complications in children and adolescents with sickle cell disease. Respiratory problems are the leading causes of sickness and of death in sickle cell disease. The investigators hypothesize that daily oral vitamin D3, compared to monthly oral vitamin D, will rapidly increase circulating vitamin D3, and reduce the rate of respiratory complications by 50% or more within the first year of supplementation in children and adolescents with sickle cell disease. This study is funded by the FDA Office of Orphan Products Development (OOPD).

Mechanisms of Dupilumab in AERD
Aspirin-exacerbated Respiratory DiseaseAspirin-Exacerbated Respiratory Disease (AERD), although uncommon in the general population, is an important phenotype of severe asthma and nasal polyposis where it occurs in 15% of severe asthmatics, and up to 30% of those with nasal polyposis. An important therapy for AERD is aspirin therapy after desensitization (ADAT). This is an inexpensive and proven therapy to improve the burden of sinus disease in AERD. Aspirin desensitization is the mechanism by which tolerance is induced in AERD patients. This is a 1-2 day outpatient procedure whereby increasing doses of aspirin are administered and the patients invariably experience some degree of hypersensitivity reactions. It is important to understand the effect of medications on the aspirin desensitization. It is known that the leukotriene modifier medications decrease the severity of the reactions in AERD. Other treatments such as antihistamines and the biologic agent omalizumab might have an effect on either blocking or blunting reactivity in AERD during desensitization. Dupilumab is a new respiratory biologic approved for atopic dermatitis, eosinophilic asthma and nasal polyposis. As such, it is well situated to be used for many AERD patients whose disease cannot be well controlled. The effect of dupilumab on the aspirin desensitization process and reaction is unknown and is the topic of this investigation. The primary objective is to determine the effect of dupilumab on reactions during aspirin challenge/desensitization.

Study of the Evolution of Olfactory Disorders in Patients With Persistent Loss of Smell Following...
SARS-CoV-2 Acute Respiratory DiseaseThe COVID-19 pandemic is a novel medical challenge, particularly because of the systemic nature of this disease. Indeed, COVID-19 affects several organs and systems at once. The brain is affected in several ways: direct infection of nerve cells by SARS-CoV-2, inflammation of the central nervous system, severe systemic inflammation damaging nerve cells, global cerebral ischaemia related to respiratory failure, thromboembolic events related to increased intravascular coagulation and severe psychological stress. As a result, COVID-19 sometimes manifests as neurological and neuropsychiatric symptoms such as dizziness, sleep disturbances, cognitive deficits, delirium, or severe depression. Sudden loss of smell is a common symptom associated with COVID-19 and SARS-CoV-2 infection of neurons in the olfactory system has been reported in both hamsters and humans. The vast majority of COVID-19 patients recover their olfactory function within a few weeks. However, a significant minority of infected individuals (1 in 5 cases) still suffers from olfactory disorders (anosmia, hyposmia and/or parosmia) several months after the primary infection. These olfactory disorders are frequently associated with depressive behaviour and cognitive complaints. In PET scans, it is even possible to correlate this cognitive dysfunction with hypometabolism of certain brain regions, including the olfactory gyrus. This project proposes, during one year, to evaluate and follow the evolution of the olfactory capacities of patients suffering from persistent smell disorder since one year (+/- 4 months) following COVID-19. The issue is to study the link between viral persistence in the olfactory sensory organ, chronic inflammation, and central damage to the olfactory system. The follow-up of the evolution of olfactory and neurocognitive capacities, in an integrative way by means of molecular, physiological and behavioural approaches, will inform us on the specificities of "COVID-long" and on the level of peripheral and/or central damage of the olfactory system.