Comparison of older and younger patients with ovarian cancer: A post hoc study (JGOG3016-A3) of the treatment strength and prognostic outcomes of conventional or dose-dense chemotherapy.

AIM: To evaluate changes of treatment strength and its impact on prognosis in older patients with ovarian cancer. METHODS: We compared relative dose intensity (RDI) as a representative of treatment strength, prognosis, and other features between older (≥65 years) and younger patients (<65 years) retrospectively. Seventy-seven older patients of 301 who received dose-dense-paclitaxel-carboplatin (dTC) and 93 older patients of 304 who received conventional-paclitaxel-carboplatin (cTC) from the Japanese Gynecologic Oncology Group (JGOG) 3016 clinical trial were analyzed. RESULTS: The RDI of older patients was lower than that of younger patients in cTC (87.4% vs. 90.8%, p = 0.009) but not in dTC (79.0% vs. 81.2%, p = 0.205). In both regimens, older patients had worse overall survival than younger patients: hazard ratio [HR] = 1.80; 95% confidence interval [CI]: 1.25-2.59; p = 0.001 for dTC, and HR = 1.59; 95% CI: 1.15-2.19; p = 0.04 for cTC. However, the RDI was not determined as a prognostic factor statistically. The prognostic factors identified by multivariate analysis for both regimens were clinical stage and residual disease; for dTC were age, performance status, and serum albumin; and for cTC was white blood cell count. There was no difference in neutropenia observed between age groups in either regimen. CONCLUSIONS: The RDI of older patients varies according to the administered schedule and is not always lower than that of younger patients. Older patients with comparable treatment strength to younger patients in the dTC group did not accomplish the same level of prognosis as younger patients. Other biologic factors attributable to aging may affect prognosis.

[A PATIENT WITH ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA) WHO HAD UNDERGONE TUBERCULOSIS TREATMENT TWICE].

The case subject was a 19-year-old exchange student from Thailand who had undergone tuberculosis (TB) treatment twice. Upon observing a shadow in the right upper lung, the patient was referred for examination; however, acid-fast bacteria test results were negative. Furthermore, high levels of total IgE and anti-aspergillus IgE and IgG antibodies were found. Bronchoscopy revealed inflammation with stenosis in the right superior lobar bronchus, and there was an outflow of yellow viscous sputum upon suctioning. After applying a localized steroid spray, the patient expectorated a large amount of sputum containing Aspergillus fumigatus. Upon administration of steroids and itraconazole, the conglomerate mass shadow's inner portion disappeared, and dilated bronchi appeared. Even though the diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) of Rosenberg and Patterson were not strictly satisfied, ABPA was diagnosed in conjunction with the course of treatment. It was determined that prior tubercle bacilli test results were negative, and thus the patient must have had ABPA from the onset. The symptoms eased, and the patient returned to Thailand. Although pulmonary tuberculosis and ABPA are different illnesses, they share similarities in symptoms and clinical findings. Therefore, past medical history should not be believed blindly, and it is imperative to diagnosis the condition accurately by performing appropriate tests. Furthermore, we had the opportunity to view the computed tomography images of the chest 18 years after the initial examination. In the entire lung region, findings of significant bronchiectasis were presented.

Methacholine-induced cough as an indicator of bronchodilator-responsive cough.

BACKGROUND: Cough variant asthma (CVA) is the most common cause of chronic cough and responds well to bronchodilator therapy. Previous studies on methacholine -induced cough have shown that heightened cough response due to bronchoconstriction is a feature of CVA. The aim of this study was to assess Mch-induced cough as an indicator of bronchodilator-responsive cough (BRC). METHODS: This was a single-center retrospective study of prolonged/chronic cough cases who underwent evaluation via spirometry, FeNO and bronchial challenge testing using Mch and capsaicin (C5). Resultant bronchoconstriction after Mch challenge was assessed by flow-volume curves measuring the expiratory flow of the partial flow-volume curve 40% above residual volume (PEF40) and FEV1. BRC was defined as a decrease in cough with bronchodilator therapy by 30% or more on a visual analog scoring scale. RESULTS: Of the 100 patients evaluated, 63 were diagnosed with BRC. Mch-induced cough at a decrease in PEF40 of 35% (PC35-PEF40) was predictive of BRC on AUROC analysis with an AUC of 0.82 (95% CI 0.73-0.90) and cut-off of 24. The AUC for C5, FeNO and PC20-FEV1 were 0.65, 0.47, and 0.58, respectively. CONCLUSION: Compared to C5, FeNO and PC20-FEV1, Mch-induced cough better supports a diagnosis of BRC.

How do doctors choose treatment for older gynecological cancer patients? A Japanese Gynecologic Oncology Group survey of gynecologic oncologists.

BACKGROUND: The proportion of elderly Japanese people (age ≥ 65 years) is currently 27.7%, and the average life span of women is 87.14 years, both of which are unprecedented. In gynecologic cancer, evidence of treatment for the elderly is scarce, and treatment policies are determined by each facility. The aim of the present study was to investigate the status of treatment policies for elderly patients with gynecologic cancer. METHODS: A web-based questionnaire regarding how treatment strategies are currently determined for elderly patients with gynecologic cancer was conducted on gynecologic oncologists to develop a tool for the objective evaluation of treatment policy decisions for elderly patients. RESULTS: The responses showed that 48% of the gynecologic oncologists were aware of comprehensive geriatric assessment (CGA), but only 6% had actually conducted CGA. Age, comorbidities, performance status, and pretreatment evaluations were regarded as important in determining the treatment strategy. Invasive treatments such as radical hysterectomy and para-aortic lymph node dissection tended to have age limits. CONCLUSIONS: These findings suggest that awareness of CGA is low in Japan, and that elderly people may not be given standard therapy, which highlights the importance of building on these findings by gathering further evidence and developing a new tool for predicting treatment outcomes for elderly patients with gynecologic cancer.

Repeated bronchoconstriction attenuates the cough response to bronchoconstriction in naïve guinea pigs.

BACKGROUND: Cough variant asthma (CVA) is recognized as a precursor of bronchial asthma (BA). However, the cough response to bronchoconstriction differs between these similar diseases. Repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators may impact the cough response. METHODS: We investigated the influence of repeated bronchoconstriction on the cough response to bronchoconstriction using naïve guinea pigs. Bronchoconstriction was induced for 3 consecutive days and changes in the cough response and lipid mediators, such as PGE2, PGI2, and cysteinyl-LTs (Cys-LTs), in BAL fluid (BALF) were assessed. We investigated the effect of endogenous PGI2 on the cough response by employing a PGI2 receptor antagonist. In order to investigate the cough response over a longer period, we re-evaluated the cough response 2 weeks after repeated bronchoconstriction. RESULTS: The number of coughs induced by bronchoconstriction were significantly decreased by repeated bronchoconstriction. The levels of PGE2, PGI2, and Cys-LTs, and the ratio of PGI2/PGE2 were significantly increased, following repeated bronchoconstriction. This decrease in the cough response was suppressed by pretreatment with a PGI2 receptor antagonist. Two weeks after repeated bronchoconstriction, the cough response returned to the same level as before repeated bronchoconstriction along with a concomitant return of lipid mediators, such as PGE2, PGI2, and Cys-LTs and the ratio of PGI2/PGE2. CONCLUSIONS: Our results suggest that repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators contribute to the difference in cough responses to bronchoconstriction in CVA and BA.

Effect of triple therapy in patients with asthma-COPD overlap
.

OBJECTIVE: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is of increasing interest because ACO patients have significantly worse outcomes, leading to greater social and economic burdens compared with asthma or COPD alone. Some guidelines for ACO recommend triple therapy with inhaled corticosteroids, long-acting ß2 agonists, and long-acting muscarinic antagonists. However, this approach is based on extrapolating data from patients with asthma or COPD alone. Therapeutic studies for ACO have not previously been conducted. MATERIALS AND METHODS: A 12-week, randomized, open-label cross-over pilot study was conducted in 17 ACO patients to evaluate the effect of umeclidinium (UMEC) 62.5 µg once-daily added to fluticasone furoate/vilanterol (FF/VI) 200/25 µg once-daily. A 4-week run-in, a first and a second 4-week treatment period were included. Respiratory function, respiratory impedance, fractional exhaled nitric oxide, COPD assessment test, and asthma control test scores were evaluated 0, 4, and 8 weeks after randomization. RESULTS: Mean values of post-bronchodilator forced expiratory volume in 1 second as a percentage of the predicted value (%FEV1), after UMEC was added to FF/VI, were significantly higher than after the run-in (p < 0.01). Mean values of resonant frequency during inspiration (Fres), after UMEC was added to FF/VI, were significantly lower than after the run-in (p < 0.01). CONCLUSION: Adding UMEC to FF/VI provides greater improvement in lung function, indicating that triple therapy is a suitable regular treatment for ACO.

Role of prostaglandin E2 in bronchoconstriction-triggered cough response in guinea pigs.

A feature of cough variant asthma is a heightened cough response to bronchoconstriction. The mediators of this response are unknown. This study was designed to elucidate the role of lipid mediators in bronchoconstriction-triggered cough response in an experimental animal model. We examined the influence of bronchoconstriction on cell components and mediators including prostaglandin E2 (PGE2) in bronchoalveolar lavage fluid (BALF). We studied the cough response to bronchoconstriction (CRB) by measuring the correlation between the increase in enhanced pause (Penh), an index of bronchoconstriction, and cough counts induced by methacholine (Mch) inhalation in conscious guinea pigs. We then examined the effects of intraperitoneal pretreatment with 16, 16-dimethyl-prostaglandin E2 (dm-PGE2) on CRB and cough counts. The total number of cells and cell components in the BALF were not influenced by bronchoconstriction. While levels of PGE2, prostaglandin I2, and cysteinyl leukotrienes were significantly increased, levels of prostaglandin D2, thromboxane B2, and substance P in the BALF were not. Dm-PGE2 significantly decreased the Mch-induced increase in Penh. Following bronchoconstriction by additional Mch inhalation, dm-PGE2 produced an increase in CRB and cough counts in a dose-dependent manner. Additionally, the heightened CRB following dm-PGE2 treatment was suppressed by pretreatment with PGE2 receptor (E-prostanoid EP) -1 and EP-3 antagonists in a dose-dependent manner, but not by EP-2 and EP-4 antagonists. The EP-1 antagonist also decreased cough counts. These results suggest that PGE2 acts as an exacerbating factor for bronchoconstriction-triggered cough. EP1 and EP3 may provide new therapeutic targets for cough variant asthma.

Role of prostaglandin I2 in the bronchoconstriction-triggered cough response in guinea pigs.

Purpose/Aim of the study: Methacholine chloride (MCh) inhalation causes bronchoconstriction and cough. Following MCh-induced bronchoconstriction, metabolic products of prostaglandin I2 (PGI2) increase in bronchoalveolar lavage fluid (BALF), suggesting that PGI2 plays a role in the cough response. Accordingly, we used an experimental guinea pig model to evaluate the role of PGI2 in the bronchoconstriction-triggered cough response. MATERIALS AND METHODS: Experiment 1: The concentration of PGF1α, a stable metabolite of PGI2, in BALF was assessed in animals exposed to nebulized MCh and animals exposed to nebulized saline. Experiment 2: Bronchoconstriction and cough were assessed in 3 groups of animals after MCh inhalation (a saline group, low-dose PGI2 group, and high-dose PGI2 group). Enhanced pause (Penh) was used as a measure of bronchoconstriction. Experiment 3: Bronchoconstriction and cough were assessed in 3 groups of animals (groups administered saline, a low dose of a specific antagonist of the PGI2 receptor (IP antagonist), and a high dose of a specific IP antagonist). RESULTS: The PGF1α concentration in BALF was significantly higher in the bronchoconstriction group than in the control group. In animals administered high-dose PGI2, the MCh-induced increase in Penh was significantly suppressed, and the number of coughs induced by bronchoconstriction was significantly decreased. In animals treated with a high dose of an IP antagonist, the MCh-induced increase in Penh was not affected, and the number of coughs increased. CONCLUSIONS: Our results suggest that PGI2 ameliorates a bronchoconstriction-triggered cough. The measurement and administration of PGI2 may assist in the diagnosis and treatment, respectively, of the cough response triggered by bronchoconstriction.

[Effect of Japanese Traditional Medicine, Ninjin-Youei-To(TJ-108), on the Quality of Life of Patients with Non-Small Cell Lung Cancer Receiving Outpatient Chemotherapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy, and thus, it is very important to maintain the quality of life(QOL)of these patients. Ninjin-Youei-To(TJ-108), a Japanese traditional medicine, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-108 in patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate factors influencing the QOL of these patients, we administered a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 15 patients with non-small cell lung cancer. Factors related to the overall QOL scores and other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale" were analyzed. No significant decrease in each of the evaluated factors was observed in this study.

Staphylococcus aureus enterotoxin sensitization involvement and its association with the CysLTR1 variant in different asthma phenotypes.

BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. OBJECTIVE: To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. METHODS: We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. RESULTS: A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. CONCLUSION: SE sensitization contributes to TH2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.

Contributions of the Japanese Gynecologic Oncology Group (JGOG) in Improving the Quality of Life in Women With Gynecological Malignancies.

The Japanese Gynecologic Oncology Group (JGOG) is leading Japan in the treatment of gynecological malignancies. The JGOG consists of three treatment committees focusing on uterine cervical cancer, endometrial cancer, and ovarian cancer. Each committee makes efforts to improve treatment and diagnosis. In addition, the Supportive and Palliative Care Committee was established in 2015. Novel studies of supportive care and palliative care have been initiated by this committee. Furthermore, surveys about not only treatment results such as overall survival rates but also quality of life (QOL) and cost-effectiveness assessments are performed by the ovarian cancer committee. Improvements of patients' QOL in the treatment of gynecological malignancies were divided into three concepts as follows: QOL associated with cancer treatment, health care after cancer therapy, and progression of cancer. In this review, we report the contributions and future plans for the improvement of QOL in patients with gynecological malignancies.

The measurement of cough response to bronchoconstriction induced by methacholine inhalation in healthy subjects: An examination using the Astograph method.

BACKGROUND: We demonstrated that heightened cough response to bronchoconstriction is a fundamental feature of cough variant asthma (CVA). To evaluate this physiological feature of CVA in daily clinical practice, it is necessary to clarify the cough response to bronchoconstriction in healthy subjects. We evaluated cough response to methacholine (MCh)-induced bronchoconstriction in healthy subjects. A forced oscillometry technique was used to measure airway resistance changes with Mch. METHODS: Healthy never-smokers (21 men, 20 women; mean 22.3 ± 3.7 years) participated. None had a >3-week cough history, clinically significant respiratory or cardiovascular disorders, or disorders that might put subjects at risk or influence the study results or the subjects' ability to participate. Twofold increasing concentrations of Mch chloride diluted in phosphate-buffered saline (0.039 to 160 mg/mL) were inhaled from nebulizers at 1-minute intervals during subjects' tidal breathing after the baseline respiratory resistance (Rrs) was recorded. Mch inhalation continued until Rrs reached twice the baseline value and forced expiratory volume in 1 second (FEV1) decreased to <90% of baseline value. Spirometry was measured before Mch inhalation and immediately after Rrs had increased twofold. Coughs were counted during and for 30 minutes after Mch inhalation. The cough reflex sensitivity to capsaicin was also examined. RESULTS: The number of coughs was 11.1 ± 14.3 (median, 7.0; range, 0 to 71; reference range, 0 to 39.7). There was no significant difference in the cough response between the sexes. The reproducibility of the cough response to bronchoconstriction was sufficient. No correlation existed between the bronchoconstriction-induced cough response and capsaicin cough-reflex sensitivity. CONCLUSIONS: Using the Astograph method, cough response to bronchoconstriction could be measured easily, safely and highly reproducibly in healthy subjects.

Improved quality of life in asthma patients under long-term therapy: Assessed by AHQ-Japan.

BACKGROUND AND OBJECTIVES: Assessment of the effects of long-term management on patient quality of life (QOL) would be extremely useful for determining asthma treatment strategies. However, no studies have evaluated QOL over an extended period of time. This study evaluated the changes in QOL, drug management and disease severity in the same asthma patients at an interval of approximately 9 years. METHODS: We re-surveyed asthma patients enrolled in a survey conducted in 2004 to evaluate the effects of approximately a decade of treatment on disease severity and QOL assessed by the Japanese Asthma Health Questionnaire (AHQ-JAPAN). RESULTS: A total of 2179 patients were enrolled in the study from 93 centres, and 1332 patients were included in the per-protocol analysis. Usage rates of inhaled corticosteroids (ICS) for treatment of stable asthma were over 90% at both time points. The AHQ-JAPAN total score improved significantly from 22.2±19.7 in 2004 to 19.7±19.9 in 2013 (P<.001). Significant improvements were also observed in 5 of 6 subscales of AHQ-JAPAN, with Social Activity constituting the sole exception. CONCLUSIONS: Asthma severity declined and QOL assessed by AHQ-JAPAN improved, which is considered as a reflection of improved asthma control at least partly attributable to widespread use of anti-inflammatory drugs as represented by ICS. The study also revealed the presence of those with poor QOL, especially in patients with concomitant respiratory diseases, and an increase in severe persistent asthma cases, warranting further long-term efforts at improving QOL. TRIAL REGISTRATION NUMBER: UMIN 000010483.

Bronchoconstriction-triggered cough in atopic cough: A retrospective study.

BACKGROUND: Atopic cough (AC) and cough variant asthma (CVA) were identified as major causes of chronic non-productive cough in a Japanese study. A characteristic feature of CVA is the presence of a heightened cough response to bronchoconstriction. On the other hand, the cough response to bronchoconstriction in AC remains unclear. METHODS: Methacholine (Mch)-induced cough in AC was measured and compared with that in CVA. Diagnoses of AC and CVA were made based on patient history, physical examination, response to bronchodilator therapy, cough reflex sensitivity to capsaicin, spirometry, and airway responsiveness to methacholine. RESULTS: Thirteen AC patients and 12 CVA patients in whom the criteria were met were recruited to the study. After inhalation of Mch at PC35-PEF40 that means milder bronchoconstriction than PC20-FEV1, cough was triggered a few times in AC. [cough number: 1/ 32 min (0-40)]. Conversely, significantly greater number of coughs was provoked in CVA, compared with AC [cough number: 35.5/ 32 min (25-125), p < 0.05]. CONCLUSIONS: The cough response to bronchoconstriction is reduced in AC compared to CVA. This feature may be useful in the diagnosis of chronic cough.

[Effect of Japanese Traditional Medicine, TJ-48, on the Quality of Life of Patients with Non-Small Cell Lung Cancer Receiving Outpatient Chemotherapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy.It is very important to retain the quality of life (QOL) of these patients.Japanese traditional medicine, TJ-48, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-48 in patients with lung cancer undergoing outpatient chemotherapy is unknown. The present study was conducted to investigate the factors influencing the QOL of these patients. We used "The QOL questionnaire for cancer patients treated with anticancer drugs" (QOL-ACD) with 16 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other variables indicating "activity," "physical condition, "psychological condition,""social relationships," "psychological condition," and "face scale" were analyzed. Significant improvement was observed in the total QOL score, mainly owing to the improvement in the patients "physical condition."

A comparison of the efficacy of once-daily fluticasone furoate/vilanterole with twice-daily fluticasone propionate/salmeterol in asthma-COPD overlap syndrome.

BACKGROUND: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is important because patients with ACOS have significantly worse outcomes compared with those with asthma or chronic obstructive pulmonary disease (COPD) alone. Inhaled corticosteroids (ICS), together with a long-acting ß2 agonist (LABA), are recommended, but no therapeutic studies for ACOS have been conducted. Recently, fluticasone furoate/vilanterole (FF/VI) has been approved as the first once-daily ICS/LABA combination therapy for asthma and COPD. METHODS: A 12-week, randomized, open-label cross-over study was conducted in 16 patients with ACOS to compare the effectiveness of once-daily FF/VI 200/25 µg vs. twice-daily fluticasone propionate/salmeterol (FP/SAL) 500/50 µg. The study period included a 4-week run-in, the first 4-week treatment, and the second 4-week treatment. Respiratory functions, including forced expiratory volume in 1 s (FEV1) and respiratory impedance using the forced oscillation technique (FOT), were measured, as was fractional exhaled nitric oxide (FeNO). A COPD assessment test (CAT) scores and asthma control test (ACT) scores were recorded 0, 4, and 8 weeks after randomization. RESULTS: The mean values for the FEV1 were 1.33 (±0.29) L in the run-in period, 1.38 (±0.39) L after the FP/SAL treatment period, and 1.47 (±0.38) L after the FF/VI treatment period. The FEV1 value after the FF/VI treatment was significantly greater than the value after the run-in period (p < 0.01). FOT parameters, FeNO levels, CAT scores, ACT scores, and other blood tests were not significantly different during the run-in period, the FP/SAL treatment period, and the FF/VI treatment period. CONCLUSIONS: FF/VI, the first once-daily ICS/LABA, can provide substantial improvement in lung functions, indicating that FF/VI should be considered for the regular treatment of ACOS.

[Nab-Paclitaxel with platinum chemotherapy as sixth-line therapy for a non-small cell lung cancer patient].

A 48-year-old woman was admitted to our hospital for sixth-line chemotherapy. A chest X-ray film and computed tomographic (CT) scan revealed a right-sided massive tumor with multiple lung tumors. Repeated treatment with carboplatin (AUC 6) on day 1 and nab-paclitaxel (100mg/m2) on days 1, 8, and 15, every 28 days were effective in this patient. Chemotherapy with nab-paclitaxel may be effective for patients with multi-recurrent adenocarcinoma.

Beraprost, a stable analog of prostacyclin, enhances cough reflex sensitivity to capsaicin in bronchitic patients.

AIMS: Inflammatory mediators are involved in the pathophysiology of neutrophilic bronchial disorders presenting with chronic productive cough. Accumulating evidence indicates that prostanoids are key elements in the pathophysiology of these disorders. However, little is known about the role of prostacyclin in neutrophilic bronchial inflammation. METHODS: The effect of beraprost, a chemically and biologically stable analog of prostacyclin, on cough response to inhaled capsaicin was examined in 14 patients with chronic bronchitis, a neutrophilic bronchial disorder, in a randomized, placebo-controlled crossover study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of the airway cough reflex sensitivity. RESULTS: After a 2-week treatment with beraprost (80 µg twice a day orally), the cough threshold was significantly (P < .05) decreased as compared with placebo [12.2 (geometric standard error of the mean [GSEM] 1.5) µM vs. 24.4 (GSEM 1.3)]. CONCLUSIONS: These findings indicate that prostacyclin is involved in the pathophysiology of cough reflex sensitivity in patients with chronic bronchitis, a frequently encountered neutrophilic bronchial disorder presenting with chronic productive cough.