Our research unit has extensive experience in conducting clinical trials focused on patients with chronic chough. We have dedicated ourselves to advancing the understanding and treatment of this medical condition. Through our expertise and commitment, we have been able to provide excellent results to both our sponsors and the patients who participate in our trials.
Our team of researchers, physicians, and healthcare professionals works collaboratively to design and execute clinical studies that aim to explore innovative approaches to managing chronic cough. We are dedicated to conducting rigorous and ethical research, ensuring the safety and well-being of our participants throughout the trial process.
By conducting clinical trials, we strive to uncover new insights into the mechanisms underlying chronic cough and identify novel therapeutic interventions. We utilize state-of-the-art methodologies and adhere to the highest standards of scientific rigor to generate robust and reliable data.
Our mission extends beyond the research itself. We are passionate about making a meaningful impact on the lives of individuals affected by chronic cough. Through our trials, we provide patients with access to cutting-edge treatments and therapies that have the potential to alleviate their symptoms and improve their quality of life.
We take pride in our track record of delivering positive outcomes, not only to our sponsors but also to the patients who participate in our trials. Our commitment to excellence, compassion, and scientific integrity drives us to continue pushing the boundaries of knowledge and finding innovative solutions for those struggling with chronic coughing.
If you are interested in collaborating with our research unit or participating in our clinical trials, we welcome you to reach out to us. Together, we can make a difference in the lives of individuals living with chronic cough.
Coughing is a vital protective reflex that prevents aspiration and improves the clearance of the respiratory passages. It involves a complex reflex act consisting of three phases: deep inhalation, forceful exhalation with closed vocal cords, and sudden opening of the vocal cords with vigorous expulsion of sputum and foreign bodies.
However, when coughing becomes frequent and excessive, it becomes pathological. Severe coughing significantly impairs the quality of life for patients and is associated with various comorbid conditions such as incontinence, syncope, or dysphonia.
Definition of chronic cough By definition, a cough is considered chronic when it lasts for at least 8 weeks in adults and 4 weeks in children. Coughing with a duration of 3 to 8 weeks in children may also be classified as prolonged acute cough. Defining chronic cough solely based on the duration of complaints is difficult. This is because some patients cough every day for years, while others experience periods of remission. Therefore, a comprehensive clinical evaluation of the chronic cough syndrome is necessary.
Frequency of chronic cough and patient profile Chronic cough affects approximately 10% of adult patients worldwide. The frequency is higher in Europe, America, and Australia. It typically affects women around the age of 60 (two-thirds of patients). Coughing is distressing and can be triggered by various factors such as perfumes, strong odors, or changes in ambient temperature. Typical features include abnormal throat sensations (laryngeal paresthesia) and an abnormally heightened cough response to different irritants. All these characteristics are encompassed in the concept of cough hypersensitivity syndrome.
Chronic chough significantly impairs the quality of life for patients. The most common reasons for seeking medical help for chronic cough include:
The pathogenic mechanism of chronic cough is complex and not fully understood. It is believed to involve various mediators, receptors, and neural pathways. Different chemical and mechanical stimuli (gastric acid, cigarette smoke, protons, etc.) are recognized by receptors and ion channels located on the afferent nerve endings of the vagus nerve in the respiratory mucosa.
It is considered that these stimulators can enhance the influx of calcium ions, leading to the release of adenosine triphosphate (ATP). ATP activates the corresponding ATP receptors (e.g., P2X3 and P2X2/3) located on the sensory nerves of the respiratory tract. An action potential is generated and transmitted via the vagus nerve to the cough center and the central nervous system to regulate the cough reflex.
The role of ATP in the mechanism of chronic cough is increasingly being discussed. ATP is a known intracellular energy source associated with various cellular processes. It is released from cells as a result of damage (e.g., respiratory epithelium, immune cells via lysis). As early as 1972, it was hypothesized that ATP is a neurotransmitter. Since then, it has been shown that ATP stimulates afferent sensory nerve endings and the release of proinflammatory cytokines. All of this makes ATP a potential target for chronic cough therapy.
Bronchial asthma or non-asthmatic eosinophilic bronchitis Chronic cough can be a symptom in different subgroups of bronchial asthma, including classic bronchial asthma (with airflow variability and bronchial hyperresponsiveness) and cough variant asthma (with cough as the sole symptom).
Chronic cough is also present in non-asthmatic eosinophilic bronchitis, where there is no bronchoconstriction or hyperreactivity. Cough in bronchial asthma is usually dry, episodic, and triggered by strong odors, physical exertion, changes in ambient temperature, or contact with allergens. Wheezing and chest tightness are often associated.
The diagnosis of bronchial asthma is based on a comprehensive clinical evaluation of the patient, as well as the demonstration of variable airflow limitation with bronchial hyperresponsiveness, most commonly through spirometry.
Reflux-related cough A significant portion of the symptoms associated with chronic cough can be explained by the presence of reflux or aspiration. Changes in voice and taste disturbances are also characteristic. It has been found that aspiration of gastrointestinal contents provokes an inflammatory response (neutrophilic or eosinophilic).
Despite the undeniable importance of gastroesophageal reflux in chronic cough, some studies do not find significant clinical benefit from the use of proton pump inhibitors in patients with chronic cough without acid reflux and only slight benefit in those with reflux. Therefore, it is also hypothesized that gases and fluids, rather than acids, play an etiological role in chronic cough.
A high frequency of esophageal dysmotility has been documented in patients with chronic cough. This has led some authors to suggest that esophagopharyngeal reflux, rather than gastroesophageal reflux, is important in reflux-related cough.
Cough is also found in the most common allergic condition, allergic rhinitis. Approximately 47% of patients with allergic rhinitis also suffer from chronic cough, but only 11% consider it the main reason to seek medical help. The severity of allergic rhinitis correlates with the frequency of comorbid cough. Several hypotheses exist regarding the overall manifestation in the upper and lower respiratory tracts.
On one hand, this could be the rhino-bronchial reflex, with direct bronchoconstriction resulting from stimuli on the nasal mucosa (allergens).
Another explanation is the descent of secretions from the upper to the lower airways. There is also a hypothesis of generalized inflammation of the unified airway with activation and involvement of eosinophils. Due to these factors, the contemporary term for involvement of both the upper and lower airways is upper airway cough syndrome, rather than postnasal drip.
Although bronchial asthma is often associated with allergic rhinitis, there are patients with allergic rhinitis and chronic cough without evidence of asthma. Bronchial biopsies in such cases have demonstrated remodelling of the lower airways. Therefore, allergic rhinitis can lead to inflammation of the lower airways and chronic cough.
Chronic cough can be an unwanted drug reaction resulting from treatment with various medications. For example, it is observed in approximately 15% of patients receiving angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors not only lead to accumulation of kinins in the lungs but also increase the sensitivity of the cough reflex.
Bisphosphonates or calcium channel antagonists can worsen existing reflux, which can exacerbate cough. Certain eye drops (e.g., used for glaucoma treatment) can irritate the pharynx through the lacrimal duct, leading to cough.
Most respiratory diseases are characterized by the presence of cough (lung cancer, cystic fibrosis, chronic bronchitis). It is believed that cellular damage and inflammation are at the core of cough hypersensitivity.
When it comes to chronic cough, smoking undoubtedly comes to mind for both patients and physicians. It is the leading cause of chronic cough, directly associated with chronic obstructive pulmonary disease (COPD). Epidemiological studies unequivocally demonstrate the link between exposure to tobacco smoke and chronic cough.
A smoking history is a predictor of the frequency of chronic cough. However, some scientific findings shed new light on the relationship between smoking and chronic cough. For example, suppressed cough reflex following capsaicin inhalation has been observed in healthy smokers. During the first month after smoking cessation, a transient exacerbation of cough is observed (due to recovery of nicotine-damaged ciliated epithelium).
On the other hand, electronic cigarettes can induce significant suppression of the cough reflex. All these data have led some authors to “recommend” the use of electronic cigarettes as an alternative when smoking cessation is not possible, specifically due to the strong transient cough.
Despite all these causes of chronic chough, often no specific etiology is found. In such cases, it is referred to as cough hypersensitivity syndrome. The latter can be considered a diagnosis of exclusion. Chronic chough is a concerning medical issue that requires a comprehensive approach and collaboration between specialists from various fields. Many uncertainties remain regarding the mechanisms and causes of chronic cough, significantly complicating both diagnosis and subsequent treatment.
