Chronic Cough and Small Fiber Neuropathy

Study Overview
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Brief Summary
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Diabetic patients with and without chronic cough will be included in this study. After giving their informed consent, the patients will perform a spirometry, chest X-ray at the inclusion visit. Cough will be assessed using the cough visual analog scale (VAS) and the Leicester Cough Questionnaire (LCQ). Within 60 days, the patient will perform neurophysiological tests. The neurophysiological assessment will be concluded with a skin biopsy to evaluate small fiber neuropathy. The aim of the study is to compare the proportion of small fiber neuropathy between diabetic patients with chronic cough and those without chronic cough.

Detailed Description
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Chronic cough is a very common entity that affects 9.6% people worldwide. Given the high number of patients with refractory cough, the concept of cough hypersensitivity syndrome (CHS) has emerged. In CHS, afferent sensory nerves may exhibit a modification of activation patterns with facilitation of encoding signals in response to irritating stimuli. Similar patterns with neuropathic pain have been described. Small fiber neuropathy has never been assessed in chronic cough. Interestingly, diabetic patients experienced cough more frequently than healthy subject. We hypothesized that small fiber neuropathy may explain chronic cough is more frequent in diabetic patients. Within 60 days after inclusion, diabetic patients with and without chronic cough will perform neurophysiological tests such as electromyography, thermotest, QSART (Quantitative Sudomotor Axon Reflex Test and Sudoscan), cardio-vascular tests to study the autonomic nervous system. No risks are expecting with these non-invasive tests. A skin biopsy to evaluate small fiber neuropathy will also be performed.After the neurophysiological tests, a consultation will be scheduled at 6 months. A cough VAS and LCQ will be used to assess cough.

Official Title
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Chronic Cough and Small Fiber Neuropathy

Conditions
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Chronic Cough, Type 2 Diabetes

Intervention / Treatment
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* Other: Cough assessment
* Other: Neurological tests and cardiovascular tests
* Other: Skin biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In diabetic patients with chronic cough: Chronic cough defined by cough for more than 8 weeks. Normal chest X-ray history of type 2 diabetes Age of diabetes onset> 40 years Affiliated or beneficiary person of social security Free, informed and written consent In diabetic patients without chronic cough History of type 2 diabetes Age of discovery of diabetes> 40 years Affiliated or beneficiary person of social security Free, informed and written consent Exclusion Criteria: Presence of physical signs of peripheral neuropathy Active smoking or smoking cessation within the last 12 months Pregnant or lactating woman History of non-type 2 diabetes (type I, secondary diabetes, monogenic ...) Cancer within the last 5 years (except cutaneous squamous cell carcinoma) History of anti-cancer chemotherapy Suspicion of autoimmune pathology Active neurological pathology Electromyography in favor of large fiber neuropathy Chronic pathology that may interfere with the neurophysiological assessment Patient who were given anticoagulation drug therapy, anti-cholinergic drugs, beta-blocker and impossibility to withdraw the treatment before neurophysiological tests In diabetic patients without chronic cough, another non-inclusion criteria is acute or chronic cough

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Diabetic patients with chronic cough<br>Diabetic patients with chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy. | Other: Cough assessment<br>* Cough assessment with cough visual analog scale (VAS), and Leicester Cough Questionnaire (LCQ) for Diabetic patients with chronic cough and Diabetic patients without chronic cough<br>Other: Neurological tests and cardiovascular tests<br>* Neurological tests : electromyography, thermotest, QSAR + cardiovascular test for Diabetic patients with chronic cough and Diabetic patients without chronic cough<br>Other: Skin biopsy<br>* Skin biopsy to evaluate small fiber neuropathy for Diabetic patients with chronic cough and Diabetic patients without chronic cough<br>|
| Other: Diabetic patients without chronic cough<br>Diabetic patients without chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy. | Other: Cough assessment<br>* Cough assessment with cough visual analog scale (VAS), and Leicester Cough Questionnaire (LCQ) for Diabetic patients with chronic cough and Diabetic patients without chronic cough<br>Other: Neurological tests and cardiovascular tests<br>* Neurological tests : electromyography, thermotest, QSAR + cardiovascular test for Diabetic patients with chronic cough and Diabetic patients without chronic cough<br>Other: Skin biopsy<br>* Skin biopsy to evaluate small fiber neuropathy for Diabetic patients with chronic cough and Diabetic patients without chronic cough<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with small fiber neuropathy | The primary endpoint is the proportion of patients with small fiber neuropathy between diabetic patients with chronic cough and those without chronic cough (defined by at least 2 abnormal neurophysiological tests). | 6 month after inclusion visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with abnormal results of the thermotest | estimate the proportion of patients with abnormal results of the thermotest in each arm (with and without chronic cough) | 6 month after inclusion visit | 
| proportion of patients with pathological results of the sudori-motor response | estimate the proportion of patients with pathological results of the sudori-motor response in each arm (with and without chronic cough) | 6 month after inclusion visit | 
| the proportion of patients with abnormal results of cardiovascular tests | estimate the proportion of patients with abnormal results of cardiovascular tests assessing the autonomic nervous system in in each arm (with and without chronic cough) | 6 month after inclusion visit | 
| proportion of patients with abnormal results of laser evoked potentials | estimate the proportion of patients with abnormal results of laser evoked potentials in each arm (with and without chronic cough) | 6 month after inclusion visit | 
| proportion of patients with abnormal findings of cutaneous biopsy | estimate the proportion of patients with abnormal findings of cutaneous biopsy in in each arm (with and without chronic cough) | 6 month after inclusion visit | 
| values of Leicester Cough Questionnaire (LCQ) in diabetic patients | estimate the values of Leicester Cough Questionnaire in diabetic patients with and without chronic cough. The Leicester Cough Questionnaire comprises 19 items and takes 5 to 10 minutes to complete. Each item assesses symptoms, or the impact of symptoms, over the last 2 weeks on a seven-point Likert scale. Scores in three domains (physical, psychological and social) are calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) is also calculated by adding the domain scores together. Higher scores indicate better quality of life. | 6 month after inclusion visit | 
| values of the DN4 questionnaire in diabetic patients | estimate the values of the DN4 questionnaire in diabetic patients with and without chronic cough. It allows to estimate the probability of neuropathic pain in a patient, through 4 questions divided into 10 check items. The practitioner questions or examines the patient and completes the questionnaire himself. He notes a response (yes, no) to each item. At the end of the questionnaire, he counts the answers and assigns the note 1 for each yes, and the score 0 for each no. The sum obtained gives the score of the patient, scored out of 10. | 6 month after inclusion visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cough, diabetes, small fiber neuropathy