Add-on montelukast vs double-dose budesonide in nonasthmatic eosinophilic bronchitis: a pilot study.

BACKGROUND: Budesonide at 800 µg/d is generally suggested for treatment of nonasthmatic eosinophilic bronchitis (NAEB). In asthma, adjunctive therapy with montelukast has been shown to confer addictive anti-inflammatory effects to inhaled corticosteroid (ICS). However, whether such effects could be extrapolated to NAEB is not known. OBJECTIVES: To study the efficacy and tolerability of add-on therapy with montelukast as compared to double-dose ICS in suppressing airway eosinophilia and decreasing cough severity in NAEB. METHODS: In a randomized controlled trial, 26 nonsmoking, steroid-naïve NAEB patients presenting with chronic cough were treated with 800 µg/d budesonide or 400 µg/d budesonide plus montelukast 10 mg/d for 4 weeks. Cough visual analogue scale (CVAS) and eosinophil differential ratio in induced sputum (Eos) were monitored at baseline, Week 1, 2 and 4. Adverse events during treatment were recorded. RESULTS: The two groups were comparable in age, gender distribution, cough duration, FEV(1)% predicted, FEV(1)/FEV ratio, baseline CVAS and geometric mean of Eos. Both regimens significantly reduced Eos and CVAS throughout the treatment course, with abrogation of sputum eosinophilia at end of therapy. There was no significant difference between the two groups in reduction of Eos and CVAS at all time points. Both regimens were well tolerated. CONCLUSIONS: This preliminary study demonstrated that add-on montelukast might be an effective and well tolerated alternative to the generally suggested dose of ICS in treating steroid-naive NAEB, with suppression of eosinophilic inflammation, reduction of cough severity and sparing of ICS doses. (NCT01121016).

Retrospective analysis of 76 immunocompetent patients with primary pulmonary cryptococcosis.

BACKGROUND: Pulmonary cryptococcosis typically occurs in immunocompromised patients, but it can also occur in immunocompetent patients. Our objective was to describe the clinical manifestations, diagnosis, and management of primary pulmonary cryptococcosis in immunocompetent patients. METHODS: We retrospectively reviewed the clinical data of 76 patients with primary pulmonary cryptococcosis who were admitted to our hospital from 1995 to 2010. RESULTS: Pulmonary cryptococcosis was pathologically proven in all patients. Mean patient age was 42.5 years and 55 patients (72%) were male. The major clinical manifestations were cough (47 pts, 62%), expectoration (29 pts, 38%), fever (16 pts, 21%), chest pain (15 pts, 20%), dyspnea (17 pts, 22%), and emaciation (10 pts, 13%). Eighteen patients (24%) were asymptomatic. Most patients were admitted due to shadows on chest X-rays. Lesions were more common in the lower lung (60 pts, 78.9%) than in the upper lung (25 pts, 32.9%). More lesions (28 pts, 37%) were characterized by patchy consolidations. Pulmonary cryptococcosis was confirmed histologically among all patients. Surgical removal of lesions or treatment with fluconazole and other antifungal agents for complete courses led to favorable outcomes for most patients. CONCLUSIONS: Primary pulmonary cryptococcosis was found mainly in immunocompetent patients aged <50 years without preexisting lung disease. Shadow on the chest X-ray is the predominant feature. Treatment with a complete course of fluconazole and/or other antifungal agents can achieve favorable outcome.

[Diagnostic values of the clinical characteristics of chronic cough].

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.

[Etiology and a diagnostic protocol for patients with chronic cough].

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.

[Expression and significance of severe acute respiratory syndrome associated coronavirus (SARS-CoV)-X4 protein in lungs of SARS patients].

OBJECTIVE: To investigate the significance of severe acute respiratory syndrome associated coronavirus (SARS-CoV)-X4 protein expression in lungs of patients with SARS. METHODS: Pathological features of the lungs from 4 SARS patients were examined and the expression of SARS-CoV-X4 protein in the lungs was evaluated with immunohistochemical staining using specific antibodies against protein X4. RESULTS: Microscopically, all lungs from 4 cases showed edema, erythrocyte and fibrin exudates in the alveoli, hyperplasia of alveolar epithelium, necrosis, hyaline membrane formation and fibroblast foci. Immunohistochemical stains showed a strong positivity of X4 protein in denudation cells, vascular endothelial cells and also erythrocytes and neutrophils in the alveoli of the lung tissues from the 4 cases. CONCLUSIONS: Expression of SARS-CoV-X4 protein in the lungs may be involved in the pathogenesis and progression of SARS.

[Characteristics of airway inflammatory cells and mediators in eosinophilic bronchitis patients].

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.

[The clinical features and the diagnosis of gastro-esophageal reflux induced cough].

OBJECTIVE: Gastro-esophageal reflux (GER) is an important etiological factor inducing chronic cough. This study aims to identify the clinical features for the diagnosis of GER induced cough (GERC). METHODS: A modified Irwin's diagnostic protocol and continuous 24-hour esophageal pH monitoring were performed in 50 patients with chronic cough. Twenty patients were diagnosed as having GERC. The clinical features were compared with those of non-GER (NGER) induced cough. RESULTS: One hundred and ninety-two patients met the chronic cough criteria and were fully evaluated. The x +/- s of age was (40.6 +/- 12.1) years (range, 10 - 69 years) and 101 were males and 91 were females, with a cough history of 25 months (range, 2 - 487 months). GER accounted for 10.4% (n = 20) of the causes and was the fourth common cause of chronic cough. The mean +/- SD of age was (37.7 +/- 13.9) years (range, 10 - 60 years) in the GERC group, with a cough history of 61 months (range, 3 - 360 months). Cough associated with having meals (occurring while eating or anytime during the subsequent 2 h) was present in 13 out of the 20 patients in GERC, significantly higher than that in NGER (2 out of 23 patients) (chi2= 14.29, P < 0.01). The specificity, the positive predictive value and the sensitivity of cough associated with meals for GERC were 91.3%, 86.7% and 65.0%, respectively. Regurgitation associated symptom was present in 11 out of the 20 patients in the GERC group, not significantly different from that in the NGER group (8 out of 23 patients). Continuous 24 hour ambulatory esophageal pH measurement showed that reflux events were more common in upright [8.9 (range, 1.9 - 71.9)%] than in supine position [1.4 (range, 0 - 41.2)%] as well as at post-meal [20.2 (range, 2.1 - 84.2)%] than during meal period [1.95 (range, 0 - 51.6)%] (P < 0.01 and P < 0.05). CONCLUSION: Cough associated with having meals is of diagnostic value for GERC. The reflux events are more frequent when patients are awake, with upright position and after meals.

[Clinical analysis of gastroesophageal reflux induced cough].

OBJECTIVE: To investigate the clinical features, diagnosis and management of gastroesophageal reflux induced cough (GERC). METHODS: The continuous ambulatory esophageal pH measurement was performed for 24 hour in 41 cases with chronic cough who had normal chest roentgenographic presentation, negative histamine provocation test and no abnormality of nasal cavity. The symptom association probability (SAP) was adopted to analyze the correlation of cough with gastroesophageal reflux. The anti-reflux treatment was given for 12 weeks to those patients with Demeester score >or= 14.72 and/or SAP >or= 75%. RESULTS: Twenty six out of 41 cases were diagnosed as patients with gastroesophageal reflux. The cough was completely cured in 12 cases after antireflux treatment. The SAP of cough in this cured group (proximal probe 0.75 +/- 0.21, distal probe 0.91 +/- 0.12, respectively) was significantly higher than that of patients who failed in response to antireflux treatment (proximal probe 0.36 +/- 0.31, distal probe 0.47 +/- 0.30, respectively, P < 0.05). CONCLUSION: The gastroesophageal reflux may be an independent factor which could induce chronic cough. Not only the frequency and severity of gastroesophageal reflux but also the SAP were helpful in making the diagnosis of GERC. Satisfied effect was achieved after sufficient anti-reflux treatment in patients with GERC.

[Severe acute respiratory syndrome in 78 patients: a retrospective study].

OBJECTIVE: To analyze the clinical features of severe acute respiratory syndrome (SARS) and the diagnosis and treatment of the disease. METHODS: Seventy-eight patients with SARS referred to the Guangzhou Institute of Respiratory Diseases (GIRD), China from December 22, 2002 to March 2003 were studied retrospectively. The data reviewed included those of clinical manifestations, laboratory investigation and roentgenology. RESULTS: The patients consisted of 42 men and 36 women, aged 20 - 75 years (mean 37.5 +/- 11.6 years), including 44 infected health-care professionals. Clinical symptoms of these patients were fever (100%), coughing (88%), and dyspnea (80%). Routine blood test revealed WBCs <4.0 x 10(9)/L in 12 patients (15%), (4.0 -10.0) x 10(9)/L in 49 (63%), and over 10.0 x 10(9)/L in 17 (22%) [average (7.6 +/- 5.0) x 10(9)/L]. The level of neutrophilic granulocyte was 0.75 +/- 0.13 and that of lymphocyte was 0.18 +/- 0.11. Chest X-ray and CT scanning revealed changes related to pneumonia. The transmission of the disease was likely via close contact with contagious droplets. The prevalences of acute lung injury (ALI,37 patients) and acute respiratory distress syndrome (ARDS, 21 of the 37 patients) were considerably high among the patients. Seven patients who developed ARDS complicated with MODS died. CONCLUSIONS: A history of close contact, fever, X-ray signs of pneumonia and normal or lowered WBC counts are favorable for the diagnosis of SARS. Recognition of ALI as the important index for critical SARS and comprehensive supportive management are of paramount importance in decreasing the mortality of patients with SARS.