Study of the Correlation Between Bronchial Hyperresponsiveness and Exhaled Nitric Oxide in Subjects with Suspected Symptoms of Asthma

Background: Bronchial hyperresponsiveness (BHR) is one of main features of asthma within chronic inflammation and reversible bronchoconstriction. Actually, methacholine challenge is useful method to detect BHR in subjects with suspected asthma symptoms. However, this method has some limitations due to its safety and side effects. The measure of exhaled nitric oxide (NO) demonstrates currently as the alternative method for methacholine challenge. Methods: Ninety-five subjects had at least one of the following symptoms were included in this study: wheezing or chest tightness during exercise, chronic cough, or nocturnal coughing. They were divided into two groups depending on the positivity or negativity of BHR. Lung function test, exhaled NO measurement, and methacholine challenge were done for each study subject. Results: There were no significant differences between two groups for age and male/female ratio (41 ± 22 vs 38 ± 23 years old and 0.9 vs 1.1; P > 0.05 and P > 0.05; respectively). The percentage of wheezing and nocturnal coughing in subjects with positive BHR (BHR+) was significantly higher than that in subjects with negative BHR (BHR-: 70.9% and 64.5% vs 31.2% and 45.1%; P<0.001 and P<0.01; respectively). FENO measured at 50 mL/s in subjects with BHR+ was significantly higher subjects with BHR- (36 ± 10 ppb vs 11 ± 9 ppb; P<0.001). There was a significant correlation between FENO-50 mL/s and methacholine dose in subjects with BHR+ (R= -0.695; P<0.001). FENO-50 mL/s at 35 ppb had 86.7% of sensibility and 82.9% of specificity for diagnosis of BHR. Conclusion: FENO is a useful biomarker for diagnosis of asthma in subjects with suspected symptoms of asthma. FENO level has a high sensitivity and specificity for screening out subjects with BHR. The measurement of exhaled NO may be an alternative method for detecting BHR in diagnosis of asthma in clinical practice

Delays in the diagnosis and treatment of tuberculosis patients in Vietnam: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Treatment delay is an important indicator of access to tuberculosis diagnosis and treatment. Analyses of patient delay (i.e. time interval between onset of symptoms and first consultation of a health care provider) and health care delay (i.e. time interval between first consultation and start of treatment) can inform policies to improve access. This study assesses the patient, health care provider and total delay in diagnosis and treatment of new smear-positive pulmonary tuberculosis patients, and the risk factors for long delay, in Vietnam.</p> <p>Methods</p> <p>A cross-sectional survey of new patients treated by the National Tuberculosis Control Programme was conducted in 70 randomly selected districts in Vietnam. All consecutively registered patients in one quarter of 2002 were interviewed using a pre-coded structured questionnaire.</p> <p>Results</p> <p>Median (range) delay was 4 weeks (1–48) for total, 3 (1–48) weeks for patient and 1 (0–25) week for health care delay. Patients with long total delay (≥ 12 weeks, 15%) accounted for 49% of the cumulative number of delay-weeks. Independent risk factors (p < 0.05) for long total delay were female sex, middle age, remote setting, residence in the northern or central area, and initial visit to the private sector. For long patient delay (≥ 6 weeks) this was female sex, belonging to an ethnic minority, and living at > 5 km distance from a health facility or in the northern area. For long health care delay (≥ 6 weeks) this was urban setting, residence in the central area and initial visit to a communal health post, TB hospital or the private sector.</p> <p>Conclusion</p> <p>Analyses of patient and treatment delays can indicate target groups and areas for health education and strengthening of the referral system, in particular between the private sector and the NTP.</p

Mortality and failure among tuberculosis patients who did not complete treatment in Vietnam: a cohort study

<p>Abstract</p> <p>Background</p> <p>Tuberculosis treatment failure and death rates are low in the Western Pacific Region, including Vietnam. However, failure or death may also occur among patients who did not complete treatment, i.e. reported as default or transfer-out. We aimed to assess the proportion failures and deaths among new smear-positive pulmonary tuberculosis patients with reported default or transfer-out.</p> <p>Treatment outcomes rates were 1.4% default, 3.0% transfer-out, 0.4% failure and 2.6% death in northern Vietnam in 2003.</p> <p>Methods</p> <p>Tuberculosis patients in 32 randomly selected district tuberculosis units in northern Vietnam were followed up 1 to 3 years after treatment initiation for survival, recent treatment history and bacteriologically confirmed tuberculosis.</p> <p>Results</p> <p>Included were 85 transferred patients and 42 who defaulted. No information was available of 41 (32%), 28 (22%) had died. Fifty-eight were available for follow-up (46%); all had sputum smear results. Tuberculosis was recorded in 11 (13%), including 6 (7%) with positive sputum smears, 3 (3%) with negative smears but positive culture and 2 (2%) who had started re-treatment for bacteriologically confirmed tuberculosis. Fifteen (17%, 95%CI 10–27%) had died within 8 months after treatment initiation. Of 86 patients with known study outcomes, 39 (45%, 95%CI 35–56%) had died or had bacteriologically confirmed tuberculosis. This was recorded for 29/53 (55%, 95%CI 40–68%) transferred patients and 10/33 (30%, 95%CI 16–49%) patients who defaulted.</p> <p>Conclusion</p> <p>The total failure and death rates are 0.6% and 0.8% higher than based on routine reporting in northern Vietnam. Although this was a large proportion of treatment failures and deaths, failure and death rates were low. Defaulting and transfer carry a high risk of failure and in particular death.</p

Emergence of the Asian 1 Genotype of Dengue Virus Serotype 2 in Viet Nam: In Vivo Fitness Advantage and Lineage Replacement in South-East Asia

A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs

Water-pipe smoke condensate increases the internalization of Mycobacterium Bovis of type II alveolar epithelial cells (A549)

Background: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection. Here, we studied the effects of water-pipe condense (WPC) on the internalization of Mycobacterium Bovis BCG by macropinocytosis in the alveolar epithelial cell line A549. Methods: A549 cells were exposed to WPC (4 mg/ml) for 24, 48, 72 and 96 h. Cell viability was studied using the methyl thiazolyldipenyl-tetrazolium bromide (MTT) reduction assay and proliferation by bromodeoxyUridine (BrdU) incorporation. Cells were exposed to FITC-Dextran (1 mg/ml) (as a control) and FITC-BCG (MOI = 10) for 20 min at 37 ° Cbeforecellswere collected and the uptake of BCG-FITC determined by flow cytometry. Similar experiments were performed at 4 ° Casacontrol . The Rho-associated protein kinase (ROCK) inhibitor Y-27632 (1 μ M) was used to assess the mechanism by which WPC enhanced BCG uptake. Results: WPC (4 mg/ml) increased the uptake of BCG-FITC after 72 (1.3 ± 0.1 fold, p < 0.05) and 96 (1.4 ± 0.05 fold, p < 0.05) hours. No effect on BCG-FITC uptake was observed at 24 or 48 h. WPC also significantly increased the uptake of FITC-Dextran (2.9 ± 0.3 fold, p < 0.05) after 24 h. WPC significantly decreased cell viability after 24 (84 ± 2%, p < 0.05), 48 (78±, 3%, p < 0.05), 72 (64 ± 2%, p < 0.05) and 96 h (45 ± 2%, p < 0.05). Y-27632 completely attenuated the increased uptake of BCG by WPC. Cell proliferation showed a decreasing trend in a time-dependent manner with WPC exposure. Conclusion: WPC exposure increased epithelial cell endocytosis activity and death as well as enhancing their capacity for macropinocytosis. Our in vitro data indicates possible harmful effects of WPC on the ability of lung epithelial cells to phagocytose mycobacterium

Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease

BACKGROUND: The aim of these clinical standards is to provide guidance on ‘best practice’ care for the diagnosis, treatment and prevention of post-COVID-19 lung disease. METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient’s needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session. CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease

Differential Effects of p38, MAPK, PI3K or Rho Kinase Inhibitors on Bacterial Phagocytosis and Efferocytosis by Macrophages in COPD

Pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the COPD phenotype. Small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (MAPKs), phosphatidyl-inositol-3 kinase (PI3K) and Rho kinase (ROCK) are being investigated as novel therapeutics in COPD. Concerns exist, however, about off-target effects. We investigated the effect of p38 MAPK inhibitors (VX745 and SCIO469), specific inhibitors of PI3K α (NVS-P13K-2), δ (NVS-P13K-3) or γ (NVS-P13K-5) and a ROCK inhibitor PF4950834 on macrophage phagocytosis, early intracellular killing of bacteria and efferocytosis of apoptotic neutrophils. Alveolar macrophages (AM) obtained from broncho-alveolar lavage (BAL) or monocyte-derived macrophages (MDM) from COPD patients (GOLD stage II/III) enrolled from a well characterized clinical cohort (MRC COPD-MAP consortium) or from healthy ex-smoker controls were studied. Both COPD AM and MDM exhibited lower levels of bacterial phagocytosis (using Streptococcus pneumoniae and non-typeable Haemophilus influenzae) and efferocytosis than healthy controls. None of the inhibitors altered bacterial internalization or early intracellular bacterial killing in AM or MDM. Conversely PF4950834, but not other inhibitors, enhanced efferocytosis in COPD AM and MDM. These results suggest none of these inhibitors are likely to exacerbate phagocytosis-related defects in COPD, while confirming ROCK inhibitors can enhance efferocytosis in COPD

Study of the clinical and functional characteristics of asthmatic children with obstructive sleep apnea

Yen Nguyen-Hoang,1 Thuy Nguyen-Thi-Dieu,2 Sy Duong-Quy3&ndash;5 1Department of Pediatrics, Phu Tho General Hospital, Phu Tho Province, 2Department of Pediatrics, Hanoi Medical University, Hanoi, 3Biomedical Research Center, Lam Dong Medical College, Dalat, Vietnam; 4Department of Physiology and Lung Function Testing, Cochin Hospital, Paris Descartes University, Paris, France; 5Division of Asthma and Immuno-Allergology, Hershey Medical Center, Penn State Medical College, Hershey, PA, USA Background and objective: The obstructive sleep apnea (OSA) is a common respiratory disorder in children, especially those at preschool and school ages. This study aimed to describe the characteristics of asthmatic children with OSA and the symptoms for a high risk of OSA. Subjects and methods: It was a prospective and descriptive study. The data of asthmatic children including medical history, clinical examination, blood tests, spirometry, exhaled nitric oxide (NO), and respiratory polygraphy were registered for analyses. Results: Eighty-five asthmatic children with a mean age of 9.5 &plusmn; 2.1&nbsp;years were included. The prevalence of OSA was 65.9% (56/85) in study subjects. The prevalence of severe OSA in children with moderate asthma was significantly higher than intermittent and mild asthma. The percentage of asthmatic children with OSA who had snoring, sleep disturbance, and nocturnal sweats was significantly higher than that of asthmatic children without OSA (48.2% vs 17.2%, 71.4% vs 27.5%, and 55.1% vs 31.0%, respectively). The presence of allergic rhinitis and snoring was associated significantly with a high probability for the presence of OSA. Conclusion: Children with asthma have a risk of OSA. Asthmatic children with suggested symptoms such as snoring or waking up at night should be screened for OSA. Keywords: asthma, OSA, snoring, allergic rhiniti

Exhaled Nitric Oxide as a Surrogate Marker for Obstructive Sleep Apnea Severity Grading: An In-Hospital Population Study

Khue Dang-Thi-Mai,1 Nhat-Nam Le-Dong,2 Vu Le-Thuong,1 Ngoc Tran-Van,1 Sy Duong-Quy3,4 1Department of Respiratory Diseases, Cho Ray Hospital, Ho Chi Minh City, Vietnam; 2Department of Technology, Sunrise, Namur, Belgium; 3Bio-Medical Research Centre, Lam Dong Medical College, Dalat, Vietnam; 4Penn State Medical College, Hershey Medical Center, Hershey, PA, USACorrespondence: Sy Duong-QuyBio-Medical Research Centre, Lam Dong Medical College, 16 Ngo Quyen, Dalat, VietnamTel +84 918413813Fax +84 2633815000Email [email protected]: Our study aimed to evaluate the relationship between exhaled nitric oxide (eNO) markers and obstructive sleep apnea (OSA) severity and verify the changes in eNO profiles among mild, moderate, and severe OSA subgroups.Methods: This study was a cross-sectional and in-hospital population-based study. We investigated 123 OSA patients (17 mild, 23 moderate and, 83 severe OSA) in the department of respiratory diseases. Studied data included anthropometry, respiratory polygraphy, biological markers, spirometry, and multi-flow eNO measurements. Data analysis implied linear correlation, non-parametric ANOVA, and pair-wise comparison.Results: No significant difference could be found among 3 OSA severity subgroups for FENO at &ndash; four sampling flow rates (50&ndash; 350 mL/s). The bronchial production rate of NO (J&rsquo;awNO) was proportionally increased, with median values of 11.2, 33.9, and 36.2 in mild, moderate, and severe OSA, respectively (p=0.010). The alveolar concentration of NO (CANO) changed with a non-linear pattern; it was increased in moderate (6.49) vs mild (7.79) OSA but decreased in severe OSA (5.20, p = 0.015). The only correction that could be established between OSA severity and exhaled nitric oxide markers is through J&rsquo;AWNO (rho=0.25, p=0.02) and CANO (rho= 0.18, p=0.04). There was no significant correlation between FENO measured at three different flow rates and the OSA severity. We also found a weak but significant correlation between FENO 100 and averaged SpO2 (rho = 0.07, p= 0.03).Conclusion: The present study showed that J&rsquo;AWNO, which represents eNO derived from the central airway, is proportionally increased in more severe OSA, while eNO from alveolar space, indicated by CANO, was also associated with OSA severity and relatively lower in the most severe OSA patients. In contrast, stand-alone FENO metrics did not show a clear difference among the three severity subgroups.Keywords: exhaled nitric oxide, FENO, J&rsquo;AWNO, CANO, obstructive sleep apne