Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro-oesophageal reflux and chronic cough.

Gastro-oesophageal reflux disease (GORD) is one of the most common causes of chronic cough; however, the mechanisms by which GOR initiates coughing are incompletely understood. We address the hypothesis that acidification of oesophagus acutely increases the cough reflex sensitivity in patients with GORD and chronic cough. Nine patients with GORD with chronic cough and 16 patients with GORD without cough were recruited. In a randomized double blind study, saline and acid (HCl, 0.1 mol L(-1)) were separately infused into oesophagus via naso-oesophageal catheter. Cough reflex sensitivity to inhaled capsaicin was determined immediately after completion of each infusion. Infusion of acid into oesophagus increased capsaicin cough reflex sensitivity in patients with GORD and chronic cough. In contrast, acid had no effect on the cough sensitivity in patients with GORD without cough. In a separate study, acid infusion into oesophagus did not affect the cough sensitivity in 18 healthy subjects. We conclude that acid in the oesophagus acutely increases the cough reflex sensitivity to capsaicin in patients with GORD and chronic cough. This phenomenon may contribute to the pathogenesis of cough due to GORD.

Influence of chest gamma-irradiation on cough response in awake guinea pigs.

Radiotherapy of tumors in the chest and neck regions may have serious pulmonary side effects. It is well known that inflammation is an essential manifestation of radiation-induced injury. This can heal spontaneously, by specific treatment, or it may progress to more intensive inflammation up to irreversible pulmonary fibrosis. To prevent such complications, it would be useful to have a simple non-invasive and sensitive method for monitoring the course of airway and lung post-irradiation inflammation. This study is devoted to search for such a method. We supposed that cough response intensity (CRI) could be one of the methods, which we are looking for. Guinea pigs (Trik strain, n=32) were used in the study. Animals were divided into two subgroups. Animals of a non-untreated (NT) group (n=14; M=7, F=7) were submitted to sham chest irradiation. The animals of a treated (XRT) group (n=18; M=9, F=9) were exposed to a single dose of gamma rays. Cough was provoked by exposure of animals to citric acid aerosol (CA) in gradually increasing concentrations (0.05-1.6M). CRI testing was performed two days before sham/real chest irradiation, than on 1st, 3rd, 10th, 15th, 21st, and 28th days following the day of irradiation. CRI was quantified in each animal by counting the number of coughs induced by all used concentration of CA. We found a significant increase of CRI in the animals of XRT group on 10th and 21st day compared with the NT animals. An increase of CRI also was found inside the XRT group on the 10th day after irradiation compared with the pre-irradiation value of CRI.

Tussigenic agents in the measurement of cough reflex sensitivity.

Different inhalation methods are used for cough reflex sensitivity (CRS) measurement. The single-breath method of tussigenic agent aerosol inhalation is widely used now. Comparison of two tussigenic agents--citric acid and capsaicin--in cough reflex sensitivity measurement was used in healthy volunteers. In 17 healthy volunteers (7 M, 10 F; mean age 21 years) without respiratory tract infection in last 3 weeks, without cardiovascular, allergic, respiratory metabolic diseases, and with normal spirometry, cough reflex sensitivity was examined by nebuliser ProvoJet Ganshorn Medizin Elektronic, Germany) with doubled concentrations of capsaicin (SIGMA) from 0.49 to 1000 micromol/l and citric acid (LACHEMA) concentrations of 1, 3, 10, 30, 100, 300, 1000 micromol/l. Cough reflex sensitivity was defined as the lowest concentration of tussigenic agents which elicited 2 and 5 coughs (C2, C5). Geometric mean and 95% confidence interval (CI) of citric acid C2 was 454.5 (284.8-725.4) mmol/l in 88.2% of volunteers; citric acid C5 was 1000 micromol/l (0) in 47.1% of volunteers. Capsaicin C2 was 23.5 (8.2-67.5) micromol/l in 100% of volunteers and C5 was 263.7 (111.2-625.1) micromol/l in 76.5% of volunteers. We conclude that capsaicin single-breath test is more relevant for cough reflex sensitivity measurement in healthy volunteers than citric acid cough test.

Effects of thorax irradiation on citric acid-induced cough in guinea pigs.

Thoracic irradiation may cause an acute lymphocytic alveolitis or hypersensitivity pneumonitis. It is well known that cough reflex is sensitized by a number of inflammatory mediators. The purpose of the present study was to investigate the effect of the thoracic irradiation on the cough response in awake guinea pigs. Guinea pigs (Trik strain) were exposed to sham irradiation (n=16), a single irradiation dose of 10 Gy (n=12), and a fractionated irradiation dose (in five fractions) of 15 Gy (n=12) delivered to the thorax. Cough was induced by citric acid aerosol inhalation in gradually increasing concentrations (0.05-1.6 M) during the first week after thoracic irradiation. The cough response was expressed as a total number of coughs induced during all citric acid challenges. Irradiated animals with single dose of 10 Gy exhibited a time- dependent significant increase of citric acid-induced cough in the 6th day after irradiation compared with control animals (P=0.005), whereas cough was not altered significantly in irradiated animals with fractionated dose of 15 Gy. This study demonstrates that the increased cough response may be a determinant of the functional changes of airway nerve-endings mediating cough in the early phase after thoracic irradiation.

Changes of cough reflex sensitivity induced by cancer radiotherapy of chest and neck regions.

It is reasonable to suppose that airway mucosa can be damaged by irradiation applied to chest and neck regions. The inflammatory process is a consequence of an injury. Airway inflammation is one mechanism responsible for cough induction. So, one can suppose that radiotherapy (RT) focused on the patients' chest or neck may injure airway mucosa, which might change sensitivity of the nerve-endings mediating the cough reflex. The purpose of this study was to examine cough reflex sensitivity (CRS) in patients who underwent RT in the chest and neck regions. CRS test using capsaicin was performed in patients with breast cancer (Group A, n=19), and with lung or neck cancer in (Group B, n=14) who underwent RT. Capsaicin aerosol in doubled concentrations (0.49-1000 microM) was inhaled by a single breath. CRS was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Radiation doses ranged from 40 to 70 Gy. Capsaicin cough challenge was performed before and then in the 2(nd) and 5(th) week of RT. We observed a significantly reduced value of C2, i.e., increased cough reflex sensitivity, in Group B in the 2(nd) week of RT (P= 0.04). We conclude that CRS in the lung or neck cancer patients undergoing RT is significantly enhanced, which could result from injury to the nerve endings in airway mucosa.