Research progress of flexible pressure sensor based on MXene materials.

Flexible pressure sensors overcome the limitations of traditional rigid sensors on the surface of the measured object, demonstrating broad application prospects in fields such as sports health and vital sign monitoring due to their excellent flexibility and comfort in contact with the body. MXene, as a two-dimensional material, possesses excellent conductivity and abundant surface functional groups. Simultaneously, MXene's unique layered structure and large specific surface area offer a wealth of possibilities for preparing sensing elements in combination with other materials. This article reviews the preparation methods of MXene materials and their performance indicators as sensing elements, discusses the controllable preparation methods of MXene materials and the impact of their physical and chemical properties on their functions, elaborates on the pressure sensing mechanism and evaluation mechanism of MXene materials. Starting from the four specific application directions: aerogel/hydrogel, ink printing, thin film/electronic skin, and fiber fabric, we introduce the research progress of MXene flexible pressure sensors from an overall perspective. Finally, a summary and outlook for developing MXene flexible pressure sensors are provided.

A Network Flow Analysis of the Nitrogen Metabolism in Beijing, China.

Rapid urbanization results in high nitrogen flows and subsequent environmental consequences. In this study, we identified the main metabolic components (nitrogen inputs, flows, and outputs) and used ecological network analysis to track the direct and integral (direct + indirect) metabolic flows of nitrogen in Beijing, China, from 1996 to 2012 and to quantify the structure of Beijing's nitrogen metabolic processes. We found that Beijing's input of new reactive nitrogen (Q, which represents nitrogen obtained from the atmosphere or nitrogen-containing materials used in production and consumption to support human activities) increased from 431 Gg in 1996 to 507 Gg in 2012. Flows to the industry, atmosphere, and household, and components of the system were clearly largest, with total integrated inputs plus outputs from these nodes accounting for 31, 29, and 15%, respectively, of the total integral flows for all paths. The flows through the sewage treatment and transportation components showed marked growth, with total integrated inputs plus outputs increasing to 3.7 and 5.2 times their 1996 values, respectively. Our results can help policymakers to locate the key nodes and pathways in an urban nitrogen metabolic system so they can monitor and manage these components of the system.

Comparison of clinical characteristics of chronic cough due to non-acid and acid gastroesophageal reflux.

BACKGROUND AND OBJECTIVE: Little is known about non-acid gastroesophageal reflux-induced chronic cough (GERC). The purpose of the study is to explore the clinical characteristics of non-acid GERC. METHODS: Clinical symptoms, cough symptom score, capsaicin cough sensitivity, gastroesophageal reflux diagnostic questionnaire (GerdQ) score, findings of multichannel intraluminal impedance-pH monitoring (MII-pH) and response to pharmacological anti-reflux therapy were retrospectively reviewed in 38 patients with non-acid GERC and compared with those of 49 patients with acid GERC. RESULTS: Non-acid GERC had the similar cough character, cough symptom score, and capsaicin cough sensitivity to acid GERC. However, non-acid GERC had less frequent regurgitation (15.8% vs 57.1%, χ(2) = 13.346, P = 0.000) and heartburn (7.9% vs 32.7%, χ(2) = 7.686, P = 0.006), and lower GerdQ score (7.4 ± 1.4 vs 10.6 ± 2.1, t = -6.700, P = 0.003) than acid GERC. Moreover, MII-pH revealed more weakly acidic reflux episodes, gas reflux episodes and a higher symptom association probability (SAP) for non-acid reflux but lower DeMeester score, acidic reflux episodes and SAP for acid reflux in non-acid GERC than in acid GERC. Non-acid GERC usually responded to the standard anti-reflux therapy but with delayed cough resolution or attenuation when compared with acid GERC. Fewer patients with non-acid GERC needed an augmented acid suppressive therapy or treatment with baclofen. CONCLUSIONS: There are some differences in the clinical manifestations between non-acid and acid GERC, but MII-pH is essential to diagnose non-acid GERC.

Capsaicin-sensitive cough receptors in lower airway are responsible for cough hypersensitivity in patients with upper airway cough syndrome.

BACKGROUND: Cough hypersensitivity may be related to the pathogenesis of upper airway cough syndrome (UACS). The purpose of the study was to investigate the role of capsaicin-sensitive cough receptors on the laryngopharynx and lower airway in the cough hypersensitivity of patients with UACS. MATERIAL AND METHODS: 59 patients with UACS, 33 patients with rhinitis/sinusitis without cough, and 39 healthy volunteers were recruited for the study. Cough threshold C5, defined as the lowest concentration of capsaicin required for the induction of ≥ 5 coughs upon exposure to capsaicin, were determined at baseline and after laryngopharngeal anesthesia with lidocaine in all the subjects. After induced sputum cytology, the concentrations of histamine, prostaglandin E2 (PGE2), and calcitonin-gene-related peptide (CGPR) in the induced sputum were measured by ELISA. In 15 patients with UACS, sputum cytology and measurement of the above mediators were repeated after successful therapy. RESULTS: C5 response to capsaicin was significantly lower in the UACS group than in the rhinitis/sinusitis group and healthy control groups [3.9 (0.98, 7.8) µmol/L vs. 7.8 (3.9, 93.75) µmol/L vs. 31.2 (15.6, 62.5) µmol/L, H=40.12, P=0.000]. Laryngopharngeal anesthesia with lidocaine dramatically increased C5 to capsaicin in the subjects of all 3 groups by a similar degree, but the increase in the UACS group was still the lowest, with an increased level of histamine, PGE2, and CGRP in the induced sputum. When cough resolved with the treatment of cetirizine alone or in combination with erythromycin, the levels of CGRP and histamine in the induced sputum decreased significantly in 15 patients with UACS, with no obvious change in cell differential or concentration of PGE2 in the induced sputum. CONCLUSIONS: Laryngeal TRPV1 plays an important role in cough sensitivity, but sensitization of capsaicin-sensitive cough receptors in the lower airway may be more responsible for the cough hypersensitivity in patients with UACS.

[Optimal cut-off point of symptom association probability in the diagnosis of gastroesophageal reflux-induced chronic cough].

OBJECTIVE: To explore the optimal cut-off point of symptom association probability (SAP) in the diagnosis of gastroesophageal reflux-induced chronic cough (GERC) and therefore to improve the diagnostic accuracy. METHODS: Patients with suspected GERC consecutively referred to our respiratory clinic were enrolled into this prospective study between July 2011 and February 2013. After multi-channel intraluminal esophageal impedance and pH monitoring, SAP was calculated by associating the cough recordings on the patients' diary with the detected reflux. GERC was confirmed when there was a favorable response to the following anti-reflux therapy despite the laboratory findings. The optimal cutoff point of SAP was defined according to the highest Youden index. Then, the sensitivity, specificity, positive and negative predictive values, the area under the curve of ROC, and the Kappa value for the optimal cut-off point of SAP was calculated and compared to those of SAP standards currently used in China or generally accepted in the diagnosis of GERC. RESULTS: During the study period, 103 patients with suspected GERC were recruited. Among them, GERC was confirmed in 87 patients (84.5%), including 54 patients (62.1%) due to acid reflux and 33 patients (37.9%) due to non-acid reflux. The optimal cut-off point of SAP was defined at ≥ 80% based on the highest Youden index of 0.372. For the diagnosis of GERC, SAP ≥ 80% had the area under the curve of ROC of 0.686, the Kappa value of 0.264, the sensitivity of 74.7%, the specificity of 62.5%, positive predictive value of 91.5% and negative predictive value of 31.3% respectively, which were superior to those of SAP ≥ 75% currently used in China, and to those of SAP ≥ 95% ( the generally accepted cut-off) in that the balance between higher sensitivity and higher specificity was maintained. When combined with DeMeester score ≥ 12.7, the diagnostic accuracy of SAP ≥ 80% was further improved, with the area under the curve of ROC of 0.820, the Kappa value of 0.689, the sensitivity of 87.0%, the specificity of 76.0%, positive predictive value of 94.1% and negative predictive value of 80.0%. CONCLUSION: SAP ≥ 80% may be a more suitable standard for the diagnosis of GERC.

Successful resolution of refractory chronic cough induced by gastroesophageal reflux with treatment of baclofen.

Gastroesophageal reflux induced cough is a common cause of chronic cough, and proton pump inhibitors are a standard therapy. However, the patients unresponsive to the standard therapy are difficult to treat and remain a challenge to doctors. Here, we summarized the experience of successful resolution of refractory chronic cough due to gastroesophageal reflux with baclofen in three patients. It is concluded that baclofen may be a viable option for gastroesophageal reflux induced cough unresponsive to proton pump inhibitor therapy.

[The diagnostic value of multichannel intraluminal esophageal impedance and pH monitoring in gastroesophageal reflux-related cough].

OBJECTIVE: To evaluate the diagnostic value and limitation of multichannel intraluminal esophageal impedance and pH (MII-pH) monitoring on the diagnosis of gastroesophageal reflux-related chronic cough (GERC). METHODS: The patients with suspicious GERC consecutively referred to our respiratory clinic between May 2010 and July 2011 underwent a MII-pH monitoring, and received anti-reflux drug therapy, irrespective of the laboratory findings. Chronic cough due to gastroesophageal reflux was determined when there was a favorable response to anti-reflux therapy. Then, the sensitivity, specificity, false positive and negative rate, total consistence, positively and negatively predictive value, the area under the curve of ROC and the Kappa value of the laboratory investigation were calculated for the diagnosis of GERC. RESULTS: During the research period, 56 patients completed MII-pH monitoring. Among them, the abnormal reflux was found in 35 patients, and GERC was finally confirmed in 30 patients (85.7%) including 25 patients (83.3%) due to acid reflux and 5 patients (16.7%) due to non-acid reflux. In the remaining 21 patients with normal reflux episodes, 6 patients (28.6%) could be explained by non-acid reflux for their cough because of a relatively predominant weakly acid reflux and favorable response to empirical anti-reflux therapy. For the diagnosis of GERC, MII-pH monitoring had the sensitivity of 83.3%, the specificity of 75.0%, false positive rate of 25.0%, false negative rate of 16.7%, total consistence of 80.4%, positive predictive value of 85.7%, negative predictive value of 71.4%, the area under the curve of ROC of 0.792 and Kappa value of 0.577 respectively. CONCLUSION: MII-pH is a sensitive and reliable tool for the diagnosis of GERC due to its ability to detect both acid and non-acid reflux.

[The ultrastructural features of sputum deposition and its value in the diagnosis of pulmonary alveolar proteinosis].

OBJECTIVE: To investigate the ultrastructural features of sputum deposition (SD) and its value in the diagnosis of pulmonary alveolar proteinosis (PAP). METHODS: Seven patients with PAP diagnosed by lung biopsy and cytology were enrolled in this study. The patients consisted of 5 men and 2 women, whose median age was 48 years (range 36 to 73). SD and bronchoalveolar lavage fluid (BALF) sediment were made into ultrathin sections and observed under transmission electron microscope (TEM), respectively. Seven cases of control group composed of 4 men and 3 women whose median age was 49 years (range 39 to 68) including 3 cases of bacterial pneumonia, two cases of COPD and 2 cases of exudative pulmonary tuberculosis. Each SD was made into ultrathin section, and compared with the experimental group. RESULTS: In PAP group, Periodic acid-schiff (PAS) staining was performed on 7 sputum smears and none of them was tested positive for any components with diagnostic interest. Four cases from the 7 paraffin-embed sections of BALF sediment by microscopic examination suggested PAP. Under TEM, BALF sediment showed that many lamellar bodies existed in and outside alveolar epithelial cells, and 5 specimens were consistent with PAP diagnosis. Compared with BALF sediment, SD had apparent degeneration with more myelin phagosomes in the cytoplasm of macrophages, more lamellar bodies in alveolar epithelial cells, and lots of lamellar bodies in the shape of concentric circle in the extracellular spaces. Four from the 7 SD samples were consistent with the diagnosis of PAP. No significant difference was found between SD and BALF in the diagnosis of PAP by electronic examination (P > 0.05). In the 7 cases of control group no drifting osmiophilic lamellar bodies in extracellular space were detected. CONCLUSIONS: The osmiophilic lamellar bodies with diagnostic value were found in SD and BALF of patients with PAP. TEM of SD in combination with clinical manifestations and radiologic findings can make a definitive diagnosis of PAP, especially for those patients who have contraindications to lung biopsy and lung lavage.

Empiric treatment of chronic cough in adults.

Cause-directed treatment is the mainstay of the current diagnostic approaches for chronic cough. However, empiric therapy has also been advocated in several recent guidelines for the management of chronic cough in adults. This study was designed to evaluate the usefulness of empiric therapy for chronic cough in adults. A literature review is given to discuss the issues related to empiric therapy for chronic cough in adults, including the benefits and limitations of empiric therapy, empiric treatment for the common causes of chronic cough, and the selection of management strategies. Empiric therapy for chronic cough in adults, because of its simplicity and less expense, provides the convenience for doctors in the clinics with limited facilities. It can be used either alone or in combination. When used properly, it can avoid the excessive laboratory investigations and reach the therapeutic success rate similar to cause-directed treatment. Empiric therapy is a simple and useful means for the management of chronic cough in adults and can be used as a surrogate for cause-directed therapy.

Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non-acid gastro-oesophageal reflux.

BACKGROUND AND OBJECTIVE: The aim of this study was to explore the pathogenesis of chronic cough caused by non-acid reflux. METHODS: Seven patients with chronic cough due to non-acid reflux, 12 patients with chronic cough due to acid reflux, 10 patients with gastro-oesophageal reflux disease without cough and 12 healthy volunteers were recruited for the study. All subjects underwent oesophageal multi-channel intraluminal impedance measurements combined with pH monitoring, and assessment of cough reflex sensitivity to capsaicin and induced sputum cytology. The concentrations of substance P, mast cell tryptase, prostaglandin D2 and histamine in induced sputum were measured by ELISA. RESULTS: Cough threshold C2 and C5 did not differ between patients with chronic cough due to non-acid or acid reflux, but the values were significantly lower than those for patients with gastro-oesophageal reflux disease without cough and healthy volunteers. Weakly acidic reflux episodes were obviously more frequent in patients with chronic cough due to non-acid reflux than in the other three groups. Sputum substance P and mast cell tryptase concentrations were remarkably increased in patients with chronic cough, but were similar for those with cough due to non-acid or acid reflux. There were significant inverse correlations between substance P levels and cough threshold C2 or C5 in patients with cough due to non-acid or acid reflux, and between mast cell tryptase levels and cough threshold C2 in patients with cough due to acid reflux. CONCLUSIONS: Chronic cough due to non-acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor.

Discrepancy between presumptive and definite causes of chronic cough.

BACKGROUND: The current diagnostic algorithms for chronic cough require the establishment of the primary presumptive causes followed by the confirmation of diagnosis with the specific therapies. The aim of the study was to investigate the discrepancy between presumptive and definite causes and its clinical implication. METHODS: A total of 109 patients with chronic cough underwent laboratory investigations to identify the cause of cough; including sinus computerized tomography (if needed), histamine bronchial provocation, induced sputum cytology and 24-hour esophageal pH or multi-channel intraluminal impedance combined with pH monitoring. The presumptive causes were confirmed by treating them sequentially. The difference between presumptive and definite causes of chronic cough was compared. RESULTS: Single cause was more frequent in the definite diagnosis than in the presumptive diagnosis (78.9% vs. 54.1%, χ(2) = 15.01, P = 0.0001). In contrast, multiple causes were significantly fewer in definite diagnosis than in the presumptive diagnosis (15.6% vs. 37.6%, χ(2) = 13.53, P = 0.0002). There was a discrepancy between definite and presumptive causes in 30 patients (27.5%). Compared with the presumptive causes, definite upper airway cough syndrome (24.8% vs. 11.9%, χ(2) = 6.0, P = 0.01) and gastroesophageal reflux disease (6.4% vs. 0, χ(2) = 7.23, P = 0.007) was more frequent as a single cause of chronic cough while cough variant asthma plus gastroesophageal reflux disease (3.7% vs. 11.9%, χ(2) = 5.17, P = 0.02) and upper airway cough syndrome plus nonasthmatic eosinophilic bronchitis (0 vs. 9.2%, χ(2) = 10.48, P = 0.001) were fewer as multiple causes of chronic cough. CONCLUSIONS: A discrepancy was common between presumptive and definite causes of chronic cough. To treat presumptive causes sequentially may be a suitable solution for avoidance of erroneous multiple causes and possible over-treatment.

Efficacy and safety of modified sequential three-step empirical therapy for chronic cough.

BACKGROUND AND OBJECTIVE: Sequential three-step empirical therapy is useful for the management of chronic cough. The purpose of this study was to evaluate the efficacy and safety of modified sequential three-step empirical therapy. METHODS: Consecutive patients (n = 240) with chronic cough were recruited and randomly assigned to receive modified (modified group) or primary (primary group) sequential three-step empirical therapy. The primary end-point was the overall rate of control of chronic cough. Secondary end-points were the rate of control of chronic cough at each step of therapy, the duration of treatment required, changes in cough symptom score, health-related quality of life and possible adverse effects. RESULTS: The study was completed by 106 patients in the modified group and 108 patients in the primary group. The overall rate of control of chronic cough was 88.7% in the modified group and 91.7% in the primary group (chi(2) = 0.54, P > 0.05). There were no obvious differences in the rate of control of cough at each step of therapy, the duration of treatment required, patterns of cough symptom scores or improvements in the health-related quality of life between the modified and primary groups. However, the incidence of drowsiness was significantly lower in the modified group than in the primary group (11.7% vs 21.7%, chi(2) = 4.32, P = 0.04). CONCLUSIONS: Modified three-step empirical therapy was as efficacious as primary three-step therapy for chronic cough, but was preferable because it had fewer side-effects.

Upper-airway cough syndrome with latent eosinophilic bronchitis.

Upper-airway cough syndrome often coexists with other diseases that elicit chronic cough. However, the concomitant conditions are not always relevant to chronic cough, which complicates the cause diagnosis of chronic cough. The objective of this study was to explore the diagnosis and clinical implication of upper-airway cough syndrome with latent eosinophilic bronchitis. Eleven patients with upper-airway cough syndrome and latent eosinophilic bronchitis were retrospectively analyzed for their clinical manifestations, changes of eosinophilia in induced sputum, and cough threshold with capsaicin defined as capsaicin concentration that elicits two or more coughs (C2) and five or more coughs (C5) between pretreatment and post-treatment. All patients reported a history of allergic rhinitis, showed persistent dry cough or small amounts of viscid sputum with a time course of 2-60 months (median = 7 months), and presented with symptoms and signs of rhinitis, normal lung function, and airway responsiveness. Initial eosinophil percentage in induced sputum was 3.5-8.0%. Cough disappeared after 2-5 (3 +/- 1) weeks of only oral antihistamine. With successful treatment, cough threshold C2 increased from 1.73 +/- 1.45 to 4.43 +/- 4.50 micromol/L (t = 2.64, P = 0.025) and C5 increased from 2.79 +/- 2.16 to 10.10 +/- 8.22 micromol/L (t = 3.10, P = 0.011). However, there was no significant change of eosinophil percentage in induced sputum (4.8 +/- 1.5% vs. 4.4 +/- 1.4%, t = 0.84, P = 0.427). Upper-airway cough syndrome with latent eosinophilic bronchitis is a unique condition. The recognition of the entity may avoid unnecessary use of corticosteroids.

[Changes in the spectrum and frequency of causes for chronic cough: a retrospective analysis].

OBJECTIVE: To investigate the changing patterns of the spectrum and frequency of causes for chronic cough, and to explore its clinical implications. METHODS: Nine hundred and forty patients consecutively referred to Department of Respiratory Medicine for evaluation of chronic cough between January 2004 and December 2008 were collected and divided into 5 groups by periods of 5 years. The causes of cough had been primarily evaluated according to a step-by-step protocol and confirmed by the specific therapy. The changes in spectrum and frequency of causes were retrospectively analyzed by chi2 test. RESULTS: The common causes of chronic cough were cough variant asthma (n = 437, 46%), upper airway cough syndrome/postnasal drip syndrome (n = 304, 32%), eosinophilic bronchitis (n = 87, 9%), gastroesophageal reflux-related chronic cough (n = 83, 9%), postinfectious cough (n = 60, 6%) and angiotensin-converting enzyme inhibitors-induced cough (n = 46, 5%) in descending order. There were significant differences in the distribution and frequency of etiologies when analyzed by year (chi2 = 60.6, P = 0.0001). During a 5-year period, chronic cough due to cough variant asthma increased from 44% to 51% (chi2 = 12.8, P = 0.010), upper airway cough syndrome/postnasal drip syndrome decreased from 49% to 29% (chi2 = 20.1, P = 0.001), and gastroesophageal reflux increased from 2% to 10% (chi2 = 17.6, P = 0.002). However, chronic cough associated with eosinophilic bronchitis, postinfection and angiotensin-converting enzyme inhibitors remained stable. CONCLUSION: The common causes of chronic cough vary with time, which may have an impact on the strategy for the management of chronic cough.

Changes in health-related quality of life and clinical implications in Chinese patients with chronic cough.

BACKGROUND: Chronic cough has negative effects on quality of life. However, the changes in health-related quality of life and clinical implications remain unclear in Chinese patients with chronic cough. METHODS: A standard Chinese version of Leicester cough questionnaire (LCQ) was developed by an established translation procedure and its repeatability was assessed in a preliminary study involving 20 untreated patients with stable chronic cough. The quality of life was measured with the Short form-36 health survey and compared between 110 patients with chronic cough and 90 healthy volunteers. The changes in health-related quality of life were evaluated in the patients with chronic cough with the LCQ just before the specific treatment was initiated and a week after the cough had resolved completely. Cough threshold with inhaled capsaicin, expressed as the lowest concentration of capsaicin required for the induction of > or = 5 coughs, was also measured. RESULTS: The repeatability of the Chinese version of the LCQ was validated at a four day interval with the intraclass correlation coefficients of 0.89-0.94 for total and domain score (n = 20). The scores of the Short form-36 health survey were significantly lower in patients with chronic cough than those in healthy volunteers. In general, there was no significant difference in overall quality of life between different causes of chronic cough or genders although embarrassment, frustration and sleep disturbance were more common in female patients, as indicated by the LCQ. However, the successful treatment of cough obviously increased the total scores of the LCQ from 14.2 +/- 2.7 to 19.5 +/- 1.9 (t = 13.7, P < 0.0001). There was a significant correlation between the total score of the LCQ and physical (r = 0.39, P < 0.0001) or mental (r = 0.30, P < 0.001) component summary of the Short form-36 health survey but not between the LCQ and capsaicin cough threshold. CONCLUSION: The quality of life is significantly impaired in Chinese patients with chronic cough. The Chinese version of the LCQ is a valid measure of cough related quality of life and is repeatable and responsive.

Comparison of cause distribution between elderly and non-elderly patients with chronic cough.

BACKGROUND: The causes of chronic cough in elderly patients have not been specifically investigated. Therefore, it remains to be determined whether chronic cough differs between elderly and non-elderly patients. OBJECTIVES: To investigate the distribution of causes of chronic cough in elderly patients in comparison with etiologies of chronic cough observed in non-elderly patients. METHODS: From 2,989 new patients presenting consecutively to the Department of Respiratory Medicine of the Tongji Hospital over a 1.5-year period, 287 patients with chronic cough were enrolled in the study. Patients aged > or =60 years were assigned to the elderly group. The elderly group comprised 104 patients and the non-elderly group the remaining 183 patients. The causes of cough were primarily evaluated according to a modification of Irwin's anatomic diagnostic protocol which included induced sputum cytology, verified by the specific therapy. RESULTS: Cough-variant asthma (34.6 vs. 41.5%) and upper airway cough syndrome (19.3 vs. 23.5%) were the most common causes of chronic cough both in the elderly and non-elderly groups. The distribution of causes and frequency were significantly different between elderly and non-elderly groups: angiotensin-converting enzyme inhibitor (ACEI)-induced cough (16.3 vs. 1.7%, chi(2) value = 22.12, p < 0.001) and gastroesophageal reflux disease (GERD; 10.6 vs. 3.7%, chi(2) value = 5.14, p = 0.02) were more common in the elderly group. CONCLUSIONS: A more frequent incidence of ACEI-induced cough and GERD is the distinctive feature in the cause distribution between elderly and non-elderly patients with chronic cough.

Clinical benefit of sequential three-step empirical therapy in the management of chronic cough.

BACKGROUND AND OBJECTIVE: A prospective study was conducted to investigate the efficacy of empirical therapy in the management of chronic cough. METHODS: A three-step empirical therapy protocol was used to treat patients who had a chronic cough and a normal CXR and normal lung function testing. In step one antihistamine decongestants plus bronchodilators were taken, corticosteroids in the second step, and a combination of a proton pump inhibitor and a prokinetic agent in the third step. Cough symptom scores were recorded before and after each step in the protocol. RESULTS: There were 102 patients recruited; mean age 49 +/- 16 years and with a history of cough of between 2 and 120 months at presentation. The cough resolved in 67.6% (n = 69) of the patients after the first-step therapy; in a further 12.7% (13) after the second-step therapy, and in another 7.8% (8) after the third-step of the treatment protocol. In three patients cough improved after the first-step of therapy but only achieved complete resolution when this treatment was combined with the third-step therapy. Overall, the three-step empirical therapy was successful in 88.2% (n = 90) of the patients. Cough symptom scores decreased from 3.30 +/- 0.75 to 0.30 +/- 0.97 (P < 0.001). The mean duration of treatment was 2.70 +/- 1.52 weeks (range 1-12). Cough was controlled in <4 weeks in 79.4% (n = 81) of patients. CONCLUSIONS: Three-step empirical therapy seemed to be useful in most patients and has practical application in the management of chronic cough.

Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin.

BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P < 0.05, respectively). The injection of 25 mg/kg SB207499 significantly inhibited the increased cough response and airway hyperresponsiveness, the cough frequency and PC150 in guinea pigs were (13 +/- 2) times/3 minutes and (680 +/- 81) microg/ml (P < 0.05), which differed significantly from (18 +/- 2) times/3 minutes and (400 +/- 86) microg/ml after the administration of the same dose of aminophylline (P < 0.05). The inhibition of SB207499 on cough response was dose-dependent. Similarly, SB207499 decreased the total cell number and percentage of eosinophils in bronchoalveolar lavage fluid to (2.1 +/- 0.5) x 10(6)/ml and (20 +/- 5)% respectively, which were significantly different from (3.2 +/- 0.5) x 10(6)/ml and (29 +/- 5)% in the aminophylline group (P < 0.05, respectively) or (4.2 +/- 0.7) x 10(6)/ml and (35 +/- 4)% in the challenge group (P < 0.05, respectively). CONCLUSION: Phosphodiesterase 4 inhibitor may be more useful than aminophylline for cough associated with eosinophilic airway inflammation via inhibiting airway inflammation and airway hyperresponsiveness.

[The experimental study on the inhibitory effect of tripterine on airway inflammation in asthmatic mice].

OBJECTIVE: To investigate the effect and mechanism of tripterine on airway inflammation in asthmatic mice. METHODS: 30 BALB/c mice were randomly divided into a control group, an asthmatic group (ovalbumin-sensitized) and a tripterine (1 mg/kg, introperitoneally)-treated group. Pathologic changes in lung tissues, number of eosinophils in bronchoalveolar lavage fluid (BALF) and expression of stem cell factor (SCF) protein in lung were observed. In vitro, we established coculture system of bone marrow derived-mast cells from C57B6 mice and fibroblast NIH3T3, which were then treated by 2 micro mol/L of tripterine, and compared with NIH3T3 and mast cells. Concentration of histamine and eotaxin in supernants of coculture was measured by fluorometry and ELISA respectively, and expression of SCF protein in fibroblasts from cocultures was analyzed with immunohistochemistry. RESULTS: Compared with the asthmatic group, less inflammatory cell infiltration in lung tissues was observed in the tripterine-treated group. There was significant difference in the number of eosinophils in BALF between the tripterine-treated group [(0.56 +/- 0.03) x 10(6)/L] and the asthmatic group [(1.25 +/- 0.40) x 10(6)/L, P < 0.05]. So was the expression of SCF protein in lung tissue [0.74 +/- 0.20, 2.50 +/- 0.19, P < 0.01]. In vitro, the concentration of histamine and eotaxin in coculture supernants and the expression of SCF protein in fibroblasts from coculture were (3.83 +/- 0.41) ng/ml, (5.79 +/- 0.40) ng/ml and (95 +/- 3)%, respectively; after tripterine intervention, the data changed to (2.88 +/- 0.35) ng/ml, (4.24 +/- 0.29) ng/ml, (17 +/- 5)% (all P < 0.01). CONCLUSIONS: Tripterine might suppress airway inflammation in asthmatic mice, probably by downregulating the expression of SCF in fibroblasts, then inhibiting the production of histamine and eotaxin in mast cells.