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In this extended special feature to celebrate the 35th anniversary edition of LCGC Europe, leading figures from the separation science community explore contemporary trends in separation science and identify possible future developments.

Cough sensitivity can be described as the reaction intensity of the cough reflex to different stimuli which activate chemically and mechanically sensitive vagal afferent nerves innervating airways and lungs. Measurement of cough reflex sensitivity plays an important role in revealing the underlying mechanisms of cough and evaluating the effects of pharmacological interventions. Besides, different responses to cough suppression therapies indicate the existence of cough hypersensitivity. In consideration of these factors stated above, cough sensitivity should therefore be assessed with a variety of cough challenge tests. Based on the neuroanatomical characteristics of the cough reflex, chemical challenge tests have been developed to objectively assess cough sensitivity. In cough inhalation challenges, capsaicin and citric acid are commonly used as the tussive agents to induce cough, which are validated for describing a profile of cough sensitivity to chemical irritants. Recently, mechanical methodologies have also been tried to measure the mechanical sensitivity of the cough reflex. Methodological consideration and selection are necessary for the reasonable assessment of cough sensitivity while employing cough challenges in clinical trials. Thus, in this review, we will focus on describing various methodologies of cough sensitivity measurement and, detailing some factors influencing on the accuracy of outcomes in the experimentally induced cough.

Background A higher incidence of Arnold nerve reflex (ANR) has been observed in patients with chronic cough. However, the different ANR response in various causes of chronic cough remains unclear. Furthermore, it is unknown whether ANR will change after effective treatment. Methods Patients with chronic cough were enrolled in the Guangzhou Institute of Respiratory Health. The causes of chronic cough were diagnosed via a validated management algorithm. Patients underwent an assessment of ANR response before and after 1 month of etiologic treatment. Results A total of 127 patients with chronic cough and 55 healthy control subjects were enrolled. The positive response, defined as cough-only ANR or urge-to-cough (UTC), was present in 14.8% of patients with cough variant asthma (CVA), 11.1% of patients with upper airway cough syndrome, 15.4% of patients with gastroesophageal reflex related cough (GERC), 4.8% of patients with eosinophilic bronchitis, and 26.9% of patients with unexplained cough (UC). No ANR or UTC was found in the healthy control subjects. The incidence of the positive response was higher in subjects with CVA, GERC, and UC compared with healthy control subjects (all P .05). After 1 month of treatment, 87.5% of patients identified with a positive response changed to a negative response. In a subgroup analysis, an increased cough sensitivity to capsaicin was found in the patients with a positive response compared with the patients with a negative response (P Conclusions A positive ANR appears to be a sign of vagal hypersensitivity and can be reversed after effective treatment of chronic cough. However, although various causes of chronic cough share a similar feature of an elevated ANR response in a minority of patients, there appears to be limited usefulness in assessing ANR because it does not appear to be a valid predictor of etiology of chronic cough or outcome of treatment.

Symptoms associated with lung cancer mainly consist of cancer-associated pain, cough, fatigue, and dyspnea. However, underlying mechanisms of lung cancer symptom clusters remain unclear. There remains a paucity of effective treatment to ameliorate debilitating symptoms and improve the quality of life of lung cancer survivors. Recently, extracellular ATP and its receptors have attracted increasing attention among researchers in the field of oncology. Extracellular ATP in the tumor microenvironment is associated with tumor cell metabolism, proliferation, and metastasis by driving inflammation and neurotransmission via P2 purinergic signaling. Accordingly, ATP gated P2X receptors expressed on tumor cells, immune cells, and neurons play a vital role in modulating tumor development, invasion, progression, and related symptoms. P2 purinergic signaling is involved in the development of different lung cancer-related symptoms. In this review, we summarize recent findings to illustrate the role of P2X receptors in tumor proliferation, progression, metastasis, and lung cancer- related symptoms, providing an outline of potential anti-neoplastic activity of P2X receptor antagonists. Furthermore, compared with opioids, P2X receptor antagonists appear to be innovative therapeutic interventions for managing cancer symptom clusters with fewer side effects.

A higher incidence of Arnold nerve reflex (ANR) has been observed in patients with chronic cough. However, the different ANR response in various causes of chronic cough remains unclear. Furthermore, it is unknown whether ANR will change after effective treatment.Patients with chronic cough were enrolled in the Guangzhou Institute of Respiratory Health. The causes of chronic cough were diagnosed via a validated management algorithm. Patients underwent an assessment of ANR response before and after 1 month of etiologic treatment.A total of 127 patients with chronic cough and 55 healthy control subjects were enrolled. The positive response, defined as cough-only ANR or urge-to-cough (UTC), was present in 14.8% of patients with cough variant asthma (CVA), 11.1% of patients with upper airway cough syndrome, 15.4% of patients with gastroesophageal reflex related cough (GERC), 4.8% of patients with eosinophilic bronchitis, and 26.9% of patients with unexplained cough (UC). No ANR or UTC was found in the healthy control subjects. The incidence of the positive response was higher in subjects with CVA, GERC, and UC compared with healthy control subjects (all P .05). No difference was observed among the different causes of chronic cough (all P.05). After 1 month of treatment, 87.5% of patients identified with a positive response changed to a negative response. In a subgroup analysis, an increased cough sensitivity to capsaicin was found in the patients with a positive response compared with the patients with a negative response (P .05).A positive ANR appears to be a sign of vagal hypersensitivity and can be reversed after effective treatment of chronic cough. However, although various causes of chronic cough share a similar feature of an elevated ANR response in a minority of patients, there appears to be limited usefulness in assessing ANR because it does not appear to be a valid predictor of etiology of chronic cough or outcome of treatment.