Horng-Chyuan Lin

Increased production of hydrogen peroxide and expression of CD11b/CD18 on alveolar macrophages in patients with active pulmonary tuberculosis

SETTINGnAlveolar macrophages (AM) are important in host defense against Mycobacterium tuberculosis (TB). beta 2-integrins, especially CD11a/CD18 and CD11b/CD18, are implicated in leukocyte migration, antigen presentation, phagocytosis, and production of reactive oxygen species.nnnOBJECTIVEnTo explore the functional relevance of beta 2-integrin expression to intracellular H2O2 capacity of AM in TB patients.nnnDESIGNnIn a prospective study, AM retrieved from 18 active pulmonary TB patients and 18 normal subjects were assessed for beta 2-integrin expression and intracellular H2O2 metabolism capacity by loading with anti-CD11a/CD18, anti-CD11b/CD18 monoclonal antibodies and 2,7 dichlorofluorescein diacetate (DCFH-DA) respectively, and analyzed by flow cytometry. AM from 8 normal subjects were stimulated with tumor necrosis factor-alpha (TNF-alpha, 10(5) units/ml) to examine the relationship between H2O2 production and CD11b/CD18 expression.nnnRESULTSnThe magnitude of DCFH oxidation and CD11b/CD18 expression of AM was higher in TB patients than in normal subjects. The CD11b/CD18 expression was related to the magnitude of DCFH oxidation, but not to lymphocyte numbers or subpopulations (CD4, CD8, CD25). Stimulation of AM with TNF-alpha increased H2O2 production and CD11b/CD18 expression. Pretreatment with CD11b/CD18 monoclonal antibodies inhibited TNF-alpha-induced H2O2.nnnCONCLUSIONnAM in TB patients possessed a higher capacity of oxidant metabolism. The increased CD11b/CD18 expression may be related to the increased respiratory burst response in AM against mycobacterial invasion.

Effect of nasal continuous positive airway pressure on methacholine-induced bronchoconstriction

Bronchial hyper-responsiveness is a cardinal feature of asthma. To determine whether nasal continuous positive airway pressure (NCPAP) influences airway smooth muscle in response to exogenous stimuli, we examined the effect of NCPAP on aerosolized methacholine-induced bronchoconstriction in 16 stable asthmatic patients. The dose-response curve for each subject was measured by a log transformation and linear regression analysis as well as a formula fitted to the data points to obtain values for a (slope) and b (position). The PD20FEV1 significantly increased in patients receiving 8 cmH2O of NCPAP by one doubling dose compared with that in patients using sham pressure. NCPAP shifted the dose-response curves to be flatter, deviated upwards and to the right. The coefficient a, indicating bronchial reactivity, was significantly lower in patients receiving NCPAP. The coefficient b, indicating the bronchial sensitive threshold, was higher after applying NCPAP. In contrast, coefficients a and b did not change in subjects with sham pressure. NCPAP also significantly enhanced the bronchodilator effect of inhaled salbutamol in response to methacholine-induced bronchoconstriction. In summary, we have shown that NCPAP therapy improves bronchial smooth reactivity with an increase in PD20FEV1 and a reduction in the bronchial reactivity and bronchial sensitivity. Therefore, NCPAP may provide an adjuvant therapy in patients with acute bronchial asthma.

Interleukin-5 in growth and differentiation of blood eosinophil progenitors in asthma: effect of glucocorticoids.

There are increased numbers of circulating CD34+ progenitor cells for eosinophils in patients with atopic asthma, with a further increase following allergen exposure or spontaneous worsening of asthma. We investigated the expression of IL‐5 and IL‐5Rα receptor in circulating CD34+ progenitor cells in allergic asthmatics and the effects of corticosteroids. Using double‐staining techniques, up to 50% of CD34+ cells expressed intracellular IL‐5, and by RTu2003–u2003PCR, there was significant expression of IL‐5 mRNA. When cultured in a semi‐liquid methylcellulose medium, there were more eosinophil colony‐forming units grown from asthmatic non‐adherent mononuclear cell depleted of T cells in the presence of the growth factors GM‐CSF, SCF and IL‐3, but not of IL‐5. An anti‐IL‐5Rα receptor antibody and an anti‐sense IL‐5 oligonucleotide reduced the number of eosinophil colony forming units. No IL‐5 mRNA or protein expression on T cells was observed in asthmatics or normal subjects. In the presence of growth factors including IL‐5, there were significantly greater colony numbers with eosinophilic lineage grown from either asthmatics or normal subjects. Dexamethasone (10−6u2003M) suppressed IL‐5 mRNA and protein expression in CD34+ cells, and reduced eosinophil colony‐forming units in asthmatics, but not in normal subjects. Dexamethasone did not change the expression of IL‐5Rα on CD34+ cells. We conclude that there is increased expression of IL‐5 on blood CD34+ cells of patients with asthma and that this expression may auto‐regulate eosinophilic colony formation from these progenitor cells. Corticosteroids inhibit the expression of IL‐5 in circulating CD34+ progenitor cells.

Cytoprotective response of A1, a Bcl-2 homologue expressed in mature human neutrophils and promyelocytic HL-60 cells, to oxidant stress-induced cell death.

The ability to generate reactive oxidative intermediates is one of the quintessential properties of mature human neutrophils. Endogenously generated oxidants have been shown to be an important mechanism underlying neutrophil cell death. In acute lung inflammation, newly recruited neutrophils further encounter external oxidants, including reactive oxygen and nitrogen intermediates. In our present study, we showed that A1, a constitutive and inducible Bcl-2 homologue expressed in mature circulating human neutrophils, might confer the protection from hydrogen peroxide (H(2)O(2))- and peroxynitrite (ONOO)-induced cell death. Utilizing the myeloid precursor cell line, HL-60, we further examined the hypothesis that A1 was capable of conferring cytoprotective activity against these oxidative stresses. Whereas the control-transfected HL-60 cells expressed small amounts of A1 and were sensitive to the biologically relevant, cell death-inducing oxidants, H(2)O(2) and ONOO, the stable transfectants that overexpressed A1 were significantly more tolerant. Furthermore, there was a correlation between the level of A1 expression and the antiapoptotic activity. Thus, our results suggest a cytoprotective role of A1 in mature human neutrophils under oxidant stresses in host defense and inflammation.

Effect of β2-adrenoceptor agonists on plasma potassium and cardiopulmonary responses on exercise in patients with chronic obstructive pulmonary disease

AbstractObjective: The effect of β2-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function.nMethods: To evaluate the effect of β2-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV1/FVC ratio 48.9 (2.8)%) 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise.nResults: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq·dl−1), FEV1 or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq·dl−1 and it increased after salbutamol by 0.1 mEq·dl−1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq·dl−1) compared to the saline control (3.7 mEq · dl−1) and salbutamol (3.6 mEq · dl−1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV1, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control.nConclusion: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.

Flexible Bronchoscopy with Multiple Modalities for Foreign Body Removal in Adults

Objectives Aspiration of the lower airways due to foreign body is rare in adults. This study aimed to determine the outcome of patients who received flexible bronchoscopy with different modalities for foreign body removal in the lower airways. Patients and Methods Between January 2003 and January 2014, 94 patients diagnosed with foreign body in the lower airways underwent flexible bronchoscopy with different modalities, which included forceps, loop, basket, knife, electromagnet, and cryotherapy. The clinical presentation, foreign body location and characteristics, and applications of flexible bronchoscopy were analyzed. Results Forty (43%) patients had acute aspiration, which developed within one week of foreign body entry and 54 (57%) had chronic aspiration. The most common foreign bodies were teeth or bone. More patients with chronic aspiration than those with acute aspiration were referred from the out-patient clinic (48% vs. 28%), but more patients with acute aspiration were referred from the emergency room (35% vs. 6%) and intensive care unit (18% vs. 2%). Flexible bronchoscopy with different modalities was used to remove the foreign bodies (85/94, 90%). Electromagnet or cryotherapy was used in nine patients to eliminate the surrounding granulation tissue before foreign body removal. In the nine patients with failed flexible bronchoscopy, eight underwent rigid bronchoscopy instead and one had right lower lung lobectomy for lung abscess. Conclusions Flexible bronchoscopy with multiple modalities is effective for diagnosing and removing foreign bodies in the lower respiratory airways in adults, with a high success rate (90%) and no difference between acute and chronic aspirations.

The role of the high-sensitivity C-reactive protein in patients with stable non-cystic fibrosis bronchiectasis.

Study Objectives. The aim of this study is to investigate the correlation between serum high-sensitivity C-reactive protein (hs-CRP) and other clinical tools including high-resolution computed tomography (HRCT) in patients with stable non-CF bronchiectasis. Design. A within-subject correlational study of a group of patients with stable non-CF bronchiectasis, who were recruited from our outpatient clinic, was done over a two-year period. Measurements. Sixty-nine stable non-CF bronchiectasis patients were evaluated in terms of hs-CRP, 6-minute walk test, pulmonary function tests, and HRCT. Results. Circulating hs-CRP levels were significantly correlated with HRCT scores (n = 69, r = 0.473, P < 0.001) and resting oxygenation saturation (r = −0.269, P = 0.025). HRCT severity scores significantly increased in patients with hs-CRP level of 4.26u2009mg/L or higher (mean ± SD 28.1 ± 13.1) compared to those with hs-CRP level less than 4.26u2009mg/L (31.7 ± 9.8, P = 0.004). Oxygenation saturation at rest was lower in those with hs-CRP level of 4.26u2009mg/L or higher (93.5 ± 4.4%) compared to those with hs-CRP level less than 4.26u2009mg/L (96.4 ± 1.6%, P = 0.001). Conclusion. There was a good correlation between serum hs-CRP and HRCT scores in the patients with stable non-CF bronchiectasis.

Distance-saturation product of the 6-minute walk test predicts mortality of patients with non-cystic fibrosis bronchiectasis

BackgroundnPrevious surveillance methods to monitor the prognoses of patients with bronchiectasis are too complex for use in daily practice. The 6-minute walk test (6MWT) is a simple exercise test to predict the prognosis of chronic obstructive airway disease and numerous chronic lung diseases, including idiopathic pulmonary fibrosis. No studies have investigated exercise-induced oxygen desaturation (EID) and distance-saturation product (DSP) of 6MWT to predict the prognoses of patients with bronchiectasis.nnnMethodsnThis was a prospective study to identify correlations between variables of 6MWT and mortality in patients with bronchiectasis over a 6-year period. The study cohort included 69 patients with stable non-cystic fibrosis (non-CF) bronchiectasis who were regularly evaluated for functional status via 6-minute walk distance (6MWD), spirometry, BODE index, EID, and DSP.nnnResultsnOf the 69 patients, 9 (13%) died and 60 (87%) survived during the 6-year follow-up period. The percentage of EID was higher [7 of 9 patients (78%) vs. 22 of 60 patients (27%), P=0.003] in the non-survivors group. The 6MWD (467.9±77.1 vs. 363.7±126.7 m, P=0.001) was higher in the survivors group. DSP was significantly lower in the non-survivors group (411.0±78.4 vs. 283.9±90.0 m%, P<0.001). Multivariate analysis showed that DSP (OR =0.983; 95% CI: 0.974-0.993, P=0.001) was the best parameter of 6MWT to predict mortality. Patients with a lower DSP of <280 m% were at a 66.5-fold greater risk (OR =66.5; 95% CI: 9.4-469.2) of 6-year mortality compared with those with DSP >280 m% (P<0.001).nnnConclusionsnDSP is a simple parameter to predict 6-year mortality in patients with non-CF bronchiectasis.

The Outcome of Healthcare-Associated Pseudomonas Aeruginosa Infection in Chronically Ventilated Patients in a Tertiary Care Hospital in Taiwan

Introduction: Most studies related to healthcare-associated infection with Pseudomonas aeruginosa (HAI-PA) are on acutely ventilated patients. Little is known regarding the incidence and outcomes of HAI-PA in chronically ventilated patients. This retrospective study aimed to study HAI-PA in chronically ventilated patients and the factors that affect outcome in those requiring intensive care unit (ICU) admission.Patients and Method: From 2002 to 2006, a total of 179 chronically ventilated patients and 66 patients with HAI-PA were enrolled in the study for analysis of patients characteristics and factors that predict ICU mortality when these subjects need ICU admission.Results: The median ventilated duration of all chronically ventilated patients was 206 days. Twenty four (36.4%) patients with HAI-PA needed ICU admission and 14 (58.3%) died. By multivariate analysis adjusted by age and gender after selection by bivariate analysis, APACHE II score (adjusted odds ratio, 5.23; 95% CI, 1.07 to 2.28; p=0.02), the presence of shock (adjusted odds ratio, 4.58; 95% CI, 1.21 to 2.68; p=0.03), and time to receive appropriate antibiotics (adjusted odds ratio, 3.82, 95% CI,1.01 to 2.81; p=0.05) were independent factors that predict ICU mortality of patients with HAI-PA requiring ICU admission.Conclusions: HAI-PA is not only increasing in chronic ventilated patients and but also important to their ICU admission and mortality. APACHE II scores, the presence of shock, and the time to receive appropriate antibiotics are the independent factors of mortality. Delayed treatment may cause a higher mortality and proper antibiotic treatment is important to improve outcome.

The Association of Atopy, Total IgE, and Pulmonary Function in Bronchiectasis

Background: Bronchiectasis is characterized by irreversible airway dilation and destruction, but its clinical features relative to atopy and sensitized allergens remain unclear. Therefore, this study aimed to investigate the relationship between atopy, serum IgE level, and lung function in bronchiectasis patients.Method: The study included 114 adult patients with a clinical diagnosis of bronchiectasis between January 2001 and December 2009. They were all evaluated for allergen specific-IgE levels, serum total IgE and eosinophilic cationic protein (ECP) levels, spirometry values of the pulmonary function test, and high-sensitivity C-reactive protein (hs-CRP) levels. Atopy was defined as the presence of a specific IgE to 1 or more allergens.Results: Of the 114 adult bronchiectasis patients, 33 (28.9%) showed positive specific immunoglobulin E (IgE) levels to 1 or more allergens and were assessed as atopic. Atopic patients with bronchiectasis had worse pulmonary function parameters, in terms of forced expiratory volume in 1 second (FEV1) and FEV1/FVC (forced vital capacity) ratio, and higher levels of total serum IgE. There was a significant decrease in the pulmonary function test of atopic subjects with a positive specific-IgE response to more than 2 allergens, but not in those with only 1 or 2 positive allergens. There were higher serum total IgE levels in patients with more positive allergen-specific IgE tests. Bronchiectatic patients with a high total IgE level (≥100 kU/L) had significantly worse lung function (FEV1% predicted and FEV1/FVC ratio) and more sensitized allergens than those with a normal IgE level (＜100 kU/L).Conclusion: The existence of atopy with more sensitized allergens or higher total serum IgE levels may lead to a worse pulmonary function in patients with bronchiectasis. This may be due to IgE-mediated local and systemic inflammation.