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Objective: To establish a guinea pig model of cough induced by human parainfluenza virus type 3 (PIV3) infection, and to investigate the change of the cough reflex sensitivity (CRS)., Methods: Sixty male SPF guinea pigs were divided into 6 groups (n=10, each), namely, a normal control group, an asthma group and 4 groups of PIV3 inoculation which included post-infection day (PID) 6, 12, 28, and 42. Infected animals were inoculated by intranasal instillation of PIV3 suspension. Control animals were inoculated by uninfected cell culture medium. Asthma animals were sensitized and challenged by ovalbumin. The Buxco system was used to assess cough reflex sensitivity (CRS) elicited by capsaicin and airway hyper-reaction (AHR). Airway inflammation was studied by bronchoalveolar lavage (BAL) cytology and lung histopathology., Results: The CRS of PID 6, 12, 28 and 42 groups was 7.50 (5.25), 7.30 (7.25), 8.40 (9.75) and 8.20 (5.50) Cough counts (CCnt). Compared with 2.50 (3.00) CCnt of the vehicle group, the CRS to capsaicin increased significantly in all the animals with PIV3 inoculation (P value were 0.024, 0.03, 0.011 and 0.008) and peaked in PID 42. There was no significant difference (P=0.18) between 3.90 (1.75) CCnt of the asthma animals and the normal control. Animals of PID 6 showed significantly greater AHR to 2 highest concentrations of methacholine than the normal controls. BAL total cell counts of both the PIV3-inoculated and the asthma animals were significantly higher than those of the normal control, with the number of lymphocytes increased significantly within first 2 weeks after PIV3 inoculation. The lung pathology of PIV3-inoculated animals showed airway inflammation without pneumonia in acute infectious phase., Conclusions: An animal model of cough induced by PIV3 was created. The CRS of infected guinea pigs increased significantly in both acute and subacute phases of cough. Elevation of CRS may be characteristic of cough caused by virus.

Objective: To evaluate whether the clinical characteristics of chronic cough were helpful in determining its specific causes., Methods: Patients with chronic cough were evaluated by a validated systematic diagnostic protocol. The patients with identified single cause were divided into 4 groups accordingly: cough-variant asthma (CVA), upper airway cough syndrome (UACS) or post-nasal drip syndrome (PNDS), eosinophilic bronchitis (EB), gastroesophageal reflux related cough (GERC), and the characteristics of the timing, character, onset and associated manifestations of chronic cough in different causes were compared., Results: A total of 196 patients met the inclusion criteria, including 55 with EB, 45 with UACS, 50 with CVA and 46 with GERC. No significant difference was found in age, gender and course among EB, UACS, CVA and GERC. The incidence of nocturnal cough in CVA was 26.0% (13/44), significantly higher than in EB (9.1% (5/55), chi2 = 5.272, P<0.05), UACS (2.2% (1/45), chi2 = 10.657, P<0.01) and GERC (0% (0/46), chi2 = 13.833, P<0.01). The specificity of nocturnal cough for CVA was 95.9%. The sensitivity and specificity of cough associated with meals in GERC was 52.2% (24/46) and 83.3%, and regurgitation associated symptom in GERC were 69.6% (32/46) and 80.0%, which were significantly higher than other groups. The incidence of postnasal drip, rhinitis associated symptom and case history of nasal diseases in UACS were 66.7% (30/45), 88.9% (40/45) and 82.2% (37/45), and the specificity of them were 89.4%, 65.6% and 63.6% respectively., Conclusion: The timing character and some associated symptoms of chronic cough are useful in predicting a single cause.

Objective: The spectrum and frequency of causes and the diagnostic protocol for chronic cough were explored., Methods: A total of 194 patients with at least 3 weeks of chronic cough and normal chest radiographs were recruited from the outpatient clinic of Guangzhou Institute of Respiratory Diseases between July 2003 to June 2004. The causes were investigated using a well-established protocol. The diagnostic protocol included history inquiring and physical examination, pulmonary function tests, induced sputum cell differentials, 24 h esophageal pH monitoring, CT of the paranasal sinuses or chest, fiberoptic rhinoscopy or bronchoscopy. The final diagnosis was made based on clinical manifestation, examination findings and a positive response to therapy., Results: The cause of chronic cough was defined in 95.4% of the patients, with a single cause found in 153 patients (82.7%), and multiple causes in 32 patients (17.3%). The five most important causes of cough were: eosinophilic bronchitis (n = 51, 22.4%), rhinitis and/or paranasal sinusitis (PNDs, n = 39, 17.1%), cough-variant asthma (n = 31, 13.6%), atopic cough (n = 28, 12.3%), and gastroesophageal reflux (n = 27, 11.8%)., Conclusions: The spectrum and frequency of causes of chronic cough in our study is different from the previous reports in western countries. Eosinophilic bronchitis and atopic cough are important causes of chronic cough. A modified diagnostic protocol was established accordingly.

Objective: To assess the application and the safety of capsaicin cough provocation test by dosimeter method., Methods: Capsaicin inhalation cough challenge test by dosimeter method was performed on 60 healthy volunteers (group A), 11 subjects with upper respiratory infection (group B), 10 patients with gastroesophageal reflux cough (group C) and 10 patients with asthma (group D). Each subject inhaled doubling concentrations of capsaicin (1.95, 3.90, 7.80, 15.6, 31.2, 62.5, 125, 250, 500, 1,000 micromol/L) by a breath-activated dosimeter until the concentration inducing five or more coughs (C(5)) was reached. The lg C(5) was calculated as the cough reflex sensitivity. General lung ventilation and impedance with impulse oscillometry were measured before and after the cough provocation test., Results: There was no serious side effect of the test in all subjects; two subjects complained of slight nausea; one of heartburn, and three of hoarseness. Before the provocation the values of FEV(1) in group A, B, C and D were (3.6 +/- 0.5) L, (3.7 +/- 0.7) L, (2.7 +/- 0.8) L and (2.1 +/- 0.8) L, compared with (3.6 +/- 0.5) L, (3.7 +/- 0.8) L, (2.6 +/- 0.7) L and (2.1 +/- 0.8) L after the test, the differences being not significant (all P > 0.05). Compared with the measurements after provocation, Zrs was (2.6 +/- 0.8) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.8) mm Hg.L(-1).s(-1) in group A, (2.5 +/- 0.5) mm Hg.L(-1).s(-1) vs (2.6 +/- 0.3) mm Hg.L(-1).s(-1) in group B, (2.7 +/- 0.7) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.7) mm Hg.L(-1).s(-1) in group C, (3.3 +/- 1.5) mm Hg.L(-1).s(-1) vs (3.7 +/- 2.0) mm Hg.L(-1).s(-1) in group D, the differences showed no significance (all P > 0.05 respectively). The lg C(5) value was 2.45 +/- 0.46 in group A, 2.51 +/- 0.20 in group B, 1.52 +/- 0.70 in group C, 2.34 +/- 0.56 in group D. Compared with group A, B and D, the lg C(5) value in group C was significantly different (all P < 0.01 respectively). The lg C(5) value showed no significant difference among group A, group B and group D (all P > 0.05)., Conclusion: Capsaicin inhalation cough provocation test by dosimeter method is a safe and specific tool for measuring cough reflex sensitivity.

Objective: To investigate the features of airway inflammation in patients with eosinophilic bronchitis (EB) by analyzing the inflammatory cells and mediators in induced sputum and bronchoalveolar lavage fluid (BALF)., Methods: Sputum induced by hypertonic saline aerosol inhalation was collected in 43 patients with EB (EB group), 20 patients with cough variant asthma (CVA, CVA group), 16 patients with bronchial asthma (asthma group) and 21 healthy controls (healthy group). Bronchoalveolar lavage was also performed in 11 patients with EB and 10 patients with CVA. Differential cell count was carried out in sputum and BALF. Levels of eosinophilic cationic protein (ECP), leukotriene C(4) (LTC(4)) and histamine in sputum and BALF were measured., Results: The percentage of sputum eosinophils (EOS) showed significant difference among the four groups; healthy group 0.0020 +/- 0.0050, EB group 0.1130 +/- 0.1470, CVA group 0.1900 +/- 0.1800, asthma group 0.3860 +/- 0.2670 (P < 0.01). The difference between asthma group and CVA group, and the difference between CVA group and EB group were significant (P < 0.05). The percentage of EOS in BALF was (0.011 +/- 0.016) in EB group, (0.053 +/- 0.040) in CVA group, the difference being significant (P < 0.05). The concentration of sputum ECP was (0.62 +/- 0.66) mg/L in EB group, (1.27 +/- 1.74) mg/L in CVA group, (0.07 +/- 0.10) mg/L in healthy group, the difference among the three groups being significant (P < 0.01). The difference of LTC(4) level was also significant when CVA group (0.65 +/- 0.62) microg/L was compared with EB group (0.39 +/- 0.61) microg/L (P < 0.05) and healthy group (0.15 +/- 0.11) microg/L (P < 0.01). The difference of histamine level in the supernatant of BALF was significant between CVA group (3.4 +/- 1.4) microg/L and EB group (1.6 +/- 1.5) microg/L (P < 0.05)., Conclusions: EOS infiltration is mainly localized to the central airway in EB, with lower airway levels of LTC(4) and histamine as compared to CVA. These inflammatory features may partly explain the absence of non-specific airway hyperresponsiveness in patients with EB.

Objective: To investigate the role of airway neurogenic inflammation in the pathogenesis of gastro-esophageal reflux induced cough (GERC)., Methods: Sputum was induced by hypertonic saline aerosol inhalation in 20 patients with GERC (GERC group), 10 healthy subjects (normal control group) and 8 patients with chronic cough due to other causes but complicated with gastro-esophageal reflux diseases (GERD, GERD group). Airway mucosal biopsy was performed in 6 patients with GERC and 4 patients with GERD using flexible fiberoptic bronchoscopy. The expression of substance P (SP), neurokinin 1 receptor and neurokinin A (NKA) in sputum cells and airway mucosa were detected by immunohistochemistry, and was assessed semi-quantitatively. SP, NKA, and NKB in the supernatant of induced sputum were measured with enzyme linked immunosorbent assay. Calcitonin gene-related peptide (CGRP) was measured with radioimmunoassay., Results: The concentration of SP in the supernatant of induced sputum was significantly higher in GERC group [(266 +/- 207) ng/L] than those in normal control group [(143 +/- 36) ng/L, P < 0.05] and GERD group [(130 +/- 11) ng/L, P < 0.05], and the sputum supernatant concentration of CGRP in GERC group [(180 +/- 83) ng/L] was significantly higher than those in normal control group [(105 +/- 64) ng/L, P < 0.01] and GERD group [(89 +/- 16) ng/L, P < 0.01]. The expression of SP, NK-1 receptor and NKA in induced sputum cells in GERC group were significantly higher than those in normal control group (P < 0.01, < 0.05, < 0.05) and GERD group (all P < 0.05); Expressions of SP in airway mucosa was significantly higher in GERC group than in GERD group (P < 0.01). After treatment, the concentration of CGRP in the supernatant of sputum in GERC patients was significantly lower than that before treatment (P < 0.05); the expression of SP, NK-1 and NKA in the induced sputum cells were significantly lower than that before treatment (P < 0.01, P < 0.01 or P < 0.05)., Conclusion: There is airway neurogenic inflammation in GERC patients, which maybe closely related to the development of GERC.

Objective: To explore the spectrum and frequency of causes for chronic cough in Chinese patients., Methods: 86 patients with chronic cough were enrolled in the study. The diagnostic procedure was based on the anatomical protocol for diagnosing chronic cough designed by Irwin, and additional cytological assay was performed for sputum induced by hypertonic saline aerosol inhalation. The efficacy of therapy specific to the diagnosis was evaluated., Results: Definite diagnosis was made in 77 (89.5%) out of the 86 patients with chronic cough. The most common causes included cough variant asthma (CVA) (24/86, 27.9%), postnasal drip syndrome (PNDs) (22/86, 25.6%), eosinophilic bronchitis (EB) (13/86, 15.1%), and gastroesophageal reflux (GER) (12/86, 14.0%). After active management based on the diagnosis, cough improved in 72 patients (93.5%)., Conclusions: In addition to CVA, PNDs and GER, eosinophilic bronchitis is also an important cause of chronic cough. A positive response to the specific therapy is essential to a definite diagnosis.

Objective: To study the clinical features and airway inflammation in eosinophilic bronchitis (EB) and the treatment outcomes., Methods: Irwin's anatomic protocol for diagnosing chronic cough was used in 86 patients with chronic cough, and induced sputum by hypertonic saline aerosol inhalation was performed. Differential cell counts were performed in induced sputum, and eosinophilic cationic protein (ECP) was measured with fluoroimmunoassay, while interleukin-8 (IL-8) was measured with enzyme-linked absorbed immunoassay. EB was diagnosed according to Gibson's criteria and treated with inhaled budesonide 200 - 400 micro g twice daily for four weeks, and in some patients oral prednisone 10 - 15 mg/d or methyl-prednisone 8 - 12 mg/d was given for one week., Results: 13 (15%) out of 86 patients with chronic cough were diagnosed as having EB. Dry cough was the major compliant and all had normal lung function with negative histamine provocation test. The Eos count was 0.1862 +/- 0.1632 and the concentration of ECP (2.53 +/- 2.07) mg/L in induced sputum were significant higher in patients with EB as compared with those normal subjects (P < 0.01). The cough disappeared in all patients at the end of one week of inhaled or orally administered corticosteroids., Conclusion: EB, an eosinophilic airway inflammation, is one of important causes of chronic cough and responds well to corticosteroid therapy.