Clinical challenges in managing bronchiectasis.

Bronchiectasis is a common disease in the Asia-Pacific and affected patients suffer from chronic sputum production and recurrent exacerbations. Bronchiectasis is largely idiopathic although there is diverse aetiology. The pathogenesis of bronchiectasis comprises infective, inflammatory and emzymetic elements. These interact to perpetuate continued airway damage in bronchiectasis leading to progressive airway and lung damages. Treatment of bronchiectasis is unsatisfactory and there are only very few trials. Existing data suggest some efficacy of inhaled corticosteroid therapy, which has been shown recently to clinical and anti-inflammatory properties in bronchiectasis. Immunomodulating agent such as low-dose macrolides have also been shown to have some efficacy although more data are needed to advocate their long-term usage. Antibiotic therapy is complex in bronchiectasis and includes short-term empirical treatment for acute exacerbation, and consideration of long-term maintenance of oral, nebulized and i.v. therapy. This long-neglected illness should receive more research attention in order that we can have better understanding of its aetiology, pathogenesis and treatment.

Respiratory infections unique to Asia.

Asia is a highly heterogeneous region with vastly different cultures, social constitutions and populations affected by a wide spectrum of respiratory diseases caused by tropical pathogens. Asian patients with community-acquired pneumonia differ from their Western counterparts in microbiological aetiology, in particular the prominence of Gram-negative organisms, Mycobacterium tuberculosis, Burkholderia pseudomallei and Staphylococcus aureus. In addition, the differences in socioeconomic and health-care infrastructures limit the usefulness of Western management guidelines for pneumonia in Asia. The importance of emerging infectious diseases such as severe acute respiratory syndrome and avian influenza infection remain as close concerns for practising respirologists in Asia. Specific infections such as melioidosis, dengue haemorrhagic fever, scrub typhus, leptospirosis, salmonellosis, penicilliosis marneffei, malaria, amoebiasis, paragonimiasis, strongyloidiasis, gnathostomiasis, trinchinellosis, schistosomiasis and echinococcosis occur commonly in Asia and manifest with a prominent respiratory component. Pulmonary eosinophilia, endemic in parts of Asia, could occur with a wide range of tropical infections. Tropical eosinophilia is believed to be a hyper-sensitivity reaction to degenerating microfilariae trapped in the lungs. This article attempts to address the key respiratory issues in these respiratory infections unique to Asia and highlight the important diagnostic and management issues faced by practising respirologists.

The burden of lung disease in Hong Kong: a report from the Hong Kong Thoracic Society.

BACKGROUND AND OBJECTIVE: The burden of lung disease in Hong Kong is not known. This study determined the mortality and hospitalization rates of respiratory diseases in Hong Kong in 2005, their trend in the past decade and their incidence/prevalence. METHODS: Mortality data were obtained from the Department of Health and hospitalization data from the Hospital Authority, Hong Kong. Incidence/prevalence data were obtained from local registries or local studies. Trends of mortality and hospitalization rates of various respiratory diseases from 1997 and 2005 were calculated after age standardization and were tested for significance using negative binomial regression analysis. Age standardized mortality rates in Hong Kong were compared with those of the UK and globally. RESULTS: Respiratory disease was the most common cause of mortality and hospitalization in Hong Kong in 2005. Globally and in the UK, cardiovascular disease ranked first in mortality. Respiratory infections ranked first in respiratory mortality, followed by respiratory tract cancer and chronic obstructive lung disease. Respiratory infections also ranked first followed by chronic obstructive lung disease in the utilization of respiratory inpatient bed-days. While mortality rates from all respiratory diseases decreased in the past decade, hospitalization rates remained unchanged. Unlike other respiratory diseases, mortality from respiratory infections have increased since 2001. Smoking is the most important risk factor in non-communicable respiratory diseases. CONCLUSIONS: Respiratory disease is responsible for the highest health-care burden locally. Increased efforts in improving management and prevention of these diseases, including tobacco control, improving air quality and vaccination against influenza and pneumococci, are necessary.

A cluster of cases of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Information on the clinical features of the severe acute respiratory syndrome (SARS) will be of value to physicians caring for patients suspected of having this disorder. METHODS: We abstracted data on the clinical presentation and course of disease in 10 epidemiologically linked Chinese patients (5 men and 5 women 38 to 72 years old) in whom SARS was diagnosed between February 22, 2003, and March 22, 2003, at our hospitals in Hong Kong, China. RESULTS: Exposure between the source patient and subsequent patients ranged from minimal to that between patient and health care provider. The incubation period ranged from 2 to 11 days. All patients presented with fever (temperature, >38 degrees C for over 24 hours), and most presented with rigor, dry cough, dyspnea, malaise, headache, and hypoxemia. Physical examination of the chest revealed crackles and percussion dullness. Lymphopenia was observed in nine patients, and most patients had mildly elevated aminotransferase levels but normal serum creatinine levels. Serial chest radiographs showed progressive air-space disease. Two patients died of progressive respiratory failure; histologic analysis of their lungs showed diffuse alveolar damage. There was no evidence of infection by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila. All patients received corticosteroid and ribavirin therapy a mean (+/-SD) of 9.6+/-5.42 days after the onset of symptoms, and eight were treated earlier with a combination of beta-lactams and macrolide for 4+/-1.9 days, with no clinical or radiologic efficacy. CONCLUSIONS: SARS appears to be infectious in origin. Fever followed by rapidly progressive respiratory compromise is the key complex of signs and symptoms from which the syndrome derives its name. The microbiologic origins of SARS remain unclear.

Antimicrobial resistance in Escherichia coli outpatient urinary isolates from women: emerging multidrug resistance phenotypes.

This study evaluated the antimicrobial resistance profile of outpatient urinary Escherichia coli isolated from women obtained throughout Hong Kong during 2004-2005. Of 1067 single patient isolates analyzed, 60.1% were resistant to ampicillin, 34% were resistant to co-trimoxazole, and 22.1% were resistant to ciprofloxacin. Thirty-four (6.6%) of 519 isolates in 2004 and 55 (10%) of 548 isolates in 2005 were extended-spectrum beta-lactamase (ESBL) producers with a CTX-M phenotype. Rates of non-beta-lactam resistance and ESBL production were strongly influenced by patient age. The age-stratified rates for dual co-trimoxazole and ciprofloxacin resistance and for ESBL production were 10.9% and 7.6% in women aged 18-35 years, 13% and 6.9% in women aged 36-50 years, 20.4% and 8.8% in women aged 51-64 years, and 23.7% and 11.8% in women aged > or =65 years, respectively. Nitrofurantoin and fosfomycin remain active against >90% of the isolates, irrespective of the resistance phenotypes for other drugs. Our results documented the emergence of problematic resistance phenotypes among community urinary E. coli and highlight the need to explore strategies for their containment.

Endobronchial Foreign Body Presenting as Exacerbation of Asthma.

Airway foreign bodies are a leading cause of death among children and require urgent recognition by medical personnel. While most cases are diagnosed readily from a clinical history of acute respiratory distress, some cases remain more indolent and present later. We report the case of a 7-year-old boy who aspirated a "LEGO" toy and presented with a week history of increasing respiratory distress compatible with known asthma. Despite a normal chest X-ray, a low-dose computed tomography showed the presence of a foreign body in the left main bronchus, which was subsequently removed by fiberoptic bronchoscopy. Our case serves to reemphasize the importance of considering airway foreign bodies as a cause of respiratory distress, especially in young children.

Perception of benefits and costs during SARS outbreak: An 18-month prospective study.

In this study, the authors examined perceived benefits and costs of the outbreak of severe acute respiratory syndrome (SARS). Mixed accounts of benefits and costs, rather than exclusive accounts of only benefits or costs, were proposed to be characterized by nondefensiveness and enduring changes in psychosocial resources. Participants were 70 SARS recoverers, 59 family members of SARS recoverers, and 172 healthy adults residing in Hong Kong--a SARS-affected region. Results show that participants giving an exclusive account of benefits had higher levels of defensiveness than those giving a mixed account and those giving an exclusive account of costs. Only the perceived impact of benefits given in mixed accounts were related to future accruements in personal and social resources over an 18-month period.

Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells.

Airway epithelial cells are the first targets of environmental stimuli and local cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis factor (TNF) in triggering IL-8 release has been documented previously. In this study, IL-8 mRNA and protein expression were examined in cultured human bronchial epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the presence of dexamethasone, budesonide, and fluticasone. Budesonide and fluticasone were 10-fold more potent than dexamethasone. The protein kinase C (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study shows that PKC signal pathway seems to be involved in the pyocyanin-mediated upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells. These findings suggest that a vicious cycle perpetuating inflammation may exist in the biologic milieu of bronchiectatic patients infected with Pseudomonas aeruginosa due to the production of pyocyanin. The priming action of pyocyanin appears to be blocked by glucocorticoids, thus providing in vitro data in support of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.

Severe acute respiratory syndrome: pertinent clinical characteristics and therapy.

Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus - a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003-4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation.

Ciliary central microtubular orientation is of no clinical significance in bronchiectasis.

It has been suggested that patients with bronchiectasis might have increased central microtubular orientation angle (CMOA), which leads to poor coordination of ciliary beating, and consequently impairment of airway defence. We have employed transmission electron microscopy to assess CMOA of ciliated nasal mucosa in a cohort of 133 (81F, 56.8+/-16.1yr) stable bronchiectasis and 59 healthy subjects (30F, 49.3+/-22.1yr). There was no significant difference in CMOA between bronchiectasis (13.2 degree) and control subjects (13.0 degree, P=0.82). There was no significant difference in CMOA among patients according to the etiology of bronchiectasis, presence of nasal symptoms, or sputum status of Pseudomonas aeruginosa infection. Patients with more severe bronchiectasis, i.e. those with FEV(1) <60%, FVC <60%, or more than 4 bronchiectatic lung lobes, had significantly lower CMOA than their counterparts (P<0.05). There was no correlation between CMOA with age, 24h sputum volume, exacerbation frequency, FEV(1), FVC, or the number of bronchiectatic lung lobes (P>0.05). CMOA correlated with ciliary beat frequency (negative), and the percent of cilia showing ultrastructural or microtubular defects (P<0.05). Central microtubular orientation angle does not correlate with clinically important parameters, in contrary to the results reported by previously published smaller scale studies.

Elevated levels of transforming growth factor-beta(1) in serum of patients with stable bronchiectasis.

Bronchiectasis is a chronic inflammatory and infective airway disease characterized by irreversible dilatation of the bronchi and persistent purulent sputum. Transforming growth factor-beta(1) (TGF-beta(1)) has been found to be increased in the lungs or bronchoalveolar lavage fluid of patients with inflammatory lung diseases. However, little is known on the serum TGF-beta(1) levels in patients with bronchiectasis. We aimed to determine the serum TGF-beta(1) concentrations in 95 patients with stable bronchiectasis (63 women; mean+/-sd age, 58.9+/-14.1 years) and 68 control subjects (23 women; 48.9+/-12.8 years) by ELISA, and to correlate with clinical parameters. The serum TGF-beta(1) levels were significantly higher in bronchiectatic patients compared with control subjects (median [range], 1812.5 pg/ml [1226.4-4114.5 pg/ml] vs. 1342.4 pg/ml [940.3-2371.7 pg/ml]; P<0.001). There was, however, no correlation between serum TGF-beta(1) levels with FEV(1) (% predicted), FVC (% predicted), 24h sputum volume, the number of bronchiectatic lung lobes or total white blood cell count (P>0.05). Our findings support previous indications that TGF-beta(1) may contribute to bronchiectatic airway inflammation. Further studies on the potential mechanisms and pathogenesis implications of this elevation should also be pursued in future.

Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: patterns in primary tumors and potential diagnostic application in bronchoalevolar lavage.

This study was aimed at defining patterns of aberrant gene methylation in non-small cell lung cancer (NSCLC) in Chinese patients and its use in detecting cancer cells in bronchoalveolar lavage (BAL). The methylation-specific PCR (MSP) was used to study methylation of the p16, retinoic acid receptor-beta (RARbeta), death-associated protein (DAP) kinase, and O(6)-methylguanine-DNA-methyltransferase (MGMT) genes in 75 NSCLCs [44 adenocarcinomas and 31 squamous cell carcinomas (SCCs)] and 68 BALs from suspected lung cancers. More females had adenocarcinoma than SCC (11 of 44 versus 2 of 31, P = 0.04). Aberrant methylation in at least one gene was found in 63 of 75 (84%) NSCLCs. p16, RARbeta, DAP kinase, and MGMT methylation was similar in adenocarcinoma and SCC. However, females with NSCLC showed more frequent p16 methylation than males (12 of 13 versus 36 of 62, P = 0.02), because of more frequent p16 methylation in female adenocarcinomas (10 of 11 versus 17 of 33, P = 0.02). This sexual difference was not observed in RARbeta, DAP kinase, and MGMT. At 92%, the frequency of p16 methylation in Chinese female NSCLC is one of the highest known. For BAL, MSP and cytological analysis showed concordant and discordant results in 25 of 68 and 43 of 68 samples. Of 41 MSP+/cytology- cases, 35 were eventually shown to have malignant lung lesions, 4 were at high risk but had no evidence of lung cancer, and 2 were lost to follow-up. There were two MSP-/cytology+ cases. Frequent gene methylations were seen in Chinese NSCLC patients. More frequent p16 methylation was seen in female patients. MSP is a useful molecular adjunct for cancer cell detection in BAL samples.

Exhaled and sputum nitric oxide in bronchiectasis: correlation with clinical parameters.

STUDY OBJECTIVES: Although there has been tremendous attention on endogenous nitric oxide (NO) production in many respiratory and systemic diseases, little is known on NO production in bronchiectasis. DESIGN AND SETTING: We determined exhaled and sputum NO levels in 109 patients with stable bronchiectasis (71 women; mean +/- SD age, 58.2 +/- 14.1 years) and 78 control subjects (39 women; mean age, 56.7 +/- 12.1 years) by using an automatic chemiluminescence analyzer. MEASUREMENTS AND RESULTS: There was no significant difference in exhaled NO between patients with bronchiectasis and control subjects (p = 0.11). Bronchiectasis patients with Pseudomonas aeruginosa infection had a significantly lower exhaled, but not sputum, NO levels than their counterparts and control subjects (p = 0.04 and p = 0.009, respectively). Exhaled NO correlated with 24-h sputum volume in P aeruginosa-infected patients (r = - 0.36; p = 0.002). After adjustment for sputum volume and number of bronchiectatic lung lobes, P aeruginosa-infected patients still had lower exhaled NO levels than their counterparts (p = 0.01). There was no correlation between exhaled NO with FEV(1), FVC, and the number of bronchiectatic lung lobes (p > 0.05). Sputum NO levels were not different between patients and control subjects (p = 0.64), and had no correlation with clinical parameters. CONCLUSION: Exhaled NO appears to be reduced among bronchiectasis patients with P aeruginosa infection independent of other clinical parameters, and further studies on the potential mechanisms and pathogenetic implications of this reduction should be pursued.

Validation of the Hong Kong Chinese version of the St. George Respiratory Questionnaire in patients with bronchiectasis.

STUDY OBJECTIVES: To validate the Hong Kong Chinese version of the St. George Respiratory Questionnaire (SGRQ-HK) in patients with bronchiectasis. DESIGN AND SETTING: Outpatients (93 patients; 61 women; mean age [+/- SD], 59.0 +/- 14.2 years) were assessed at baseline by the SGRQ-HK, the Hong Kong Chinese version of the 36-item short form health survey (SF-36-HK), and the hospital anxiety and depression scale (HADS). Forty randomly selected patients also were reassessed at 2 weeks for repeatability. Seventy-two patients were further reassessed at 6 months for responsiveness. MEASUREMENTS AND RESULTS: Cronbach alpha coefficients, which reflected internal consistency, were > 0.7 for all SGRQ-HK components except for symptoms (alpha = 0.59), and the intraclass correlation coefficients between baseline and the 2-week follow-up visits were between 0.80 and 0.94 (p > 0.05). SGRQ-HK component scores and total scores correlated with all the component scores of the SF-36-HK and the HADS (p < 0.02). SGRQ-HK component scores and total scores correlated with the scores of the SF-36-HK and the HADS, confirming the concurrent validity. All SGRQ-HK scores correlated negatively with FEV(1), FVC, and arterial oxygen saturation (p < 0.005), while the activity score correlated with the Karnofsky performance scale and the number of bronchiectatic lobes (p < 0.001). SGRQ-HK scores positively correlated with Borg scale scores, exacerbation frequency, and 24-h sputum volumes (p < 0.03). Patients with 24-h sputum volumes of > or = 10 mL or < 10 mL had significantly different SQRG-HK component scores and total scores (p < 0.002), although this sensitivity was not displayed by scores on the HADS or the SF-36-HK. Patients with 25% reductions in 24-h sputum volumes had significant improvements in SGRQ-HK activity scores, impact scores, and total scores (p < 0.02), but not in other quality-of-life measures or clinical parameters, indicating the responsiveness of the SGRQ-HK. CONCLUSION: The SGRQ-HK is a valid and sensitive instrument for determining quality of life in bronchiectasis patients.

Using biofunctional magnetic nanoparticles to capture gram-negative bacteria at an ultra-low concentration.

After conjugation to vancomycin (Van), chemically stable and highly magnetic anisotropic FePt magnetic nanoparticles (approximately 4 nm) become water-soluble and capture E. coli at 15 cfu mL(-1).

Computed tomographic evaluation of the role of craniofacial and upper airway morphology in obstructive sleep apnea in Chinese.

OBJECTIVES: To evaluate the relationship between cephalometric parameters, upper airway morphological factors and obstructive sleep apnea (OSA) in Chinese subjects. DESIGN: Polysomnogram (PSG) were performed and scored using standard criteria. Supine lateral cephalometric parameters and pharyngeal cross-sectional areas at the level of velopharynx (VA) and hypopharynx (HA) were measured from computed tomographic scans. The roles of these parameters and other anthropometric/demographic characteristics in OSA (apnea hypopnea index, AHI > or = 5) and their relationship with severity of OSA were explored by multiple logistic and multinominal regression analysis. RESULTS: Ninety-two subjects, ranging from normal (n = 36), mild/moderate OSA (n = 34) to severe OSA (n = 22), were evaluated. Compared with normal subjects, OSA subjects were heavier (body mass index 27 vs. 24 kg/m2) and older (47 vs. 42 years of age); had smaller VA size and VA to HA ratio, lower positioned hyoid bone, longer and thicker soft palate, and more retropositioned mandible relative to maxilla. After controlling for body mass index and age, subjects with severe OSA (AHI > 30) had more retropositioned mandible relative to maxilla (odds ratio, OR 1.31, P = 0.044) and longer soft palate (OR 1.16, P = 0.01), while those with mild/moderate OSA had larger VA to HA ratio (OR 0.17, P = 0.018). CONCLUSIONS: Craniofacial factors and upper airway morphology contributed to severity of OSA in Chinese subjects. Having controlled for obesity, more retropositioned mandible was associated with more severe OSA.

In vitro study of regulation of IL-6 production in bronchiectasis.

Persistent airway inflammation is an important pathogenetic factor in bronchiectasis, and interleukin (IL)-6 is among the mediators implicated in regulation of inflammation in bronchiectatic airways. We postulated that airway secretion with its constituents of cytokines and enzymes would provide an environment for perpetuation of inflammation in vivo. We aimed to determine the action of sputum from patients with bronchiectasis on IL-6 production from cultured normal human bronchial epithelial (NHBE) cells and its modulation by anti-inflammatory drugs in vitro. Cultures of NHBE cells were tested with (i) sputum of bronchiectatic patients, (ii) anti-tumor necrosis factor-alpha (TNF-alpha) pre-treated sputum, or (iii) recombinant human (rh)-TNF-alpha. Alternatively, NHBE cells were incubated with one of the anti-inflammatory drugs before treatment with sputum or rh-TNF-alpha. IL-6 produced into the medium was assayed by ELISA. Sputum in bronchiectasis stimulated IL-6 production from NHBE cells by 1.9 times. This was largely attributable to TNF-alpha as pre-incubation of sputum sol with anti-TNF-alpha almost neutralized the sputum effect. Apart from dexamethasone, the other drugs exerted inhibitory effects on IL-6 production. Ibuprofen suppressed sputum-stimulated IL-6 production to levels above control and effect levelled off at 50-100 microg/mi, contrasting the dose-dependent suppression to control level with MK-663 (0.1-10 microg/ml) and to sub-control levels with triptolide (20-1000 ng/ml). Our results support that sputum in bronchiectasis can stimulate IL-6 production from NHBE cells, and TNF-alpha is an important cytokine mediating the process. The suppressive effects observed with ibuprofen, triptolide and MK-663 warrant further study.

Bronchoscopy of cetaceans.

Bronchoscopy is a standard diagnostic and therapeutic procedure in respiratory medicine and has been performed on many animal species. Cetaceans suffer considerable morbidity and mortality from lower respiratory tract infections, and it is very difficult to sample lower respiratory tract secretions for microbiology and other analyses. We report our experience on performing fiberoptic bronchoscopy in three bottle-nosed dolphins (Tursiops truncatus) and one false killer whale (Pseudorca crassidens), which should help other clinicians in performing bronchoscopy in cetaceans.