CC16 levels correlate with cigarette smoke exposure in bronchial epithelial cells and with lung function decline in smokers.

BACKGROUND: Club cell protein-16 (CC16) expression has been associated with smoking-related lung function decline. The study hypothesis was that CC16 expression in both serum and bronchial epithelium is associated with lung function decline in smokers, and exposure to cigarette smoke will lead to reduction in CC16 expression in bronchial epithelial cells. METHODS: In a cohort of community-based male Chinese subjects recruited for lung function test in 2000, we reassessed their lung function ten years later and measured serum levels of CC16. CC16 expression was further assayed in bronchial epithelium from endobronchial biopsies taken from an independent cohort of subjects undergoing autofluorescence bronchoscopy, and tested for correlation between CC16 immunostaining intensity and lung function. In an in-vitro model, bronchial epithelial cells were exposed to cigarette smoke extract (CSE), and the expression levels of CC16 were measured in bronchial epithelial cells before and after exposure to CSE. RESULTS: There was a significant association between FEV1 decline and serum CC16 levels in smokers. Expression of CC16 in bronchial epithelium showed significant correlation with FEV1/FVC. Bronchial epithelial cells showed significant decrease in CC16 expression after exposure to CSE, followed by a subsequent rise in CC16 expression upon removal of CSE. CONCLUSIONS: Results of these clinical and laboratory investigations suggested that low serum CC16 was associated with smoking-related decline in lung function, demonstrated the first time in a Chinese cohort. The data also lend support to the putative role of CC16 in protection against smoking-related bronchial epithelial damage. (Abstract word count: 243) US CLINICAL TRIAL REGISTRY: NCT01185652 , first posted 20 August, 2010.

Variability of the prevalence of undiagnosed airflow obstruction in smokers using different diagnostic criteria.

PURPOSES: To estimate the prevalence of undiagnosed airflow obstruction (AFO) in Hong Kong smokers with no previous diagnosis of respiratory disease, and to assess its variability when applying different prediction equations and diagnostic criteria. METHODS: A multicenter, population-based, cross-sectional prevalence study was performed in smokers aged 20 to 80 years. Three different criteria (fixed 70% [Global Initiative for Chronic Obstructive Lung Disease and British Thoracic Society], fixed 75%, and European Respiratory Society [ERS]) were applied to define a lower limit of normal (LLN) of the FEV(1)/FVC ratio to compare with the Hong Kong Chinese reference equation (criterion 1), which had used a distribution-free method to obtain the lower fifth percentile of FEV(1)/FVC ratio as the LLN. RESULTS: In 525 male patients, using criterion 1 (local internal prediction equation) and defining AFO as FEV(1)/FVC less than LLN, the overall prevalence of AFO was 13.7%: 8.3% in age > or = 20 to 40 years, 14.0% in age > or = 40 to 60 years, and 17.8% in age > or = 60 to 80 years. When the local internal prediction equation was used as the comparison reference, the fixed-ratio methods tended to miss AFO in younger age groups and overdiagnose AFO in old age, while the ERS criteria, which uses an almost lower fifth percentile-equivalent method, showed less of such a trend but still only showed moderate agreement with criterion 1. CONCLUSIONS: Undiagnosed AFO was prevalent in Hong Kong smokers. Estimated prevalence rates were highly affected by the criteria used to define AFO. The predicted lower fifth percentile values calculated from a local reference equation as the LLN of FEV(1)/FVC ratio should be used for the diagnosis of AFO.

Pseudallescheria boydii or Aspergillus fumigatus in a lady with an unresolving lung infiltrate, and a literature review.

A 53-year-old lady with blood-stained sputum and pleuritic pain had a lingular opacity on CXR which failed to resolve. A bronchial aspirate and transbronchial biopsy revealed features of bronchocentric granulomatosis with dichotomous branching hyphae suggestive of Aspergillus infection. However, subsequent fungal culture grew Pseudallescheria boydii. This case demonstrates the similarity of clinical and histological features caused by these two fungi. This appears to be the first reported case of pulmonary pseudallescheria with a bronchocentric granulomatous response.

Updated spirometric reference values for adult Chinese in Hong Kong and implications on clinical utilization.

STUDY OBJECTIVES: The accuracy of reference values of lung function is important for assessment of severity and functional impairment of respiratory diseases. The aim of the study was to establish updated prediction formulae of spirometric parameters for Hong Kong Chinese and to compare the reference values with those derived from other studies in white and Chinese subjects. DESIGN: Cross-sectional multicenter study. SETTING: Lung function laboratories of eight regional hospitals in Hong Kong. PARTICIPANTS: Subjects were recruited by random-digit dialing. One thousand one hundred seventy-six subjects who fulfilled recruitment criteria underwent spirometry. MEASUREMENTS: Spirometry was performed according to American Thoracic Society recommendations, and the technique was standardized among the eight participating lung function laboratories. RESULTS: Evaluable data of 1,089 (494 men and 595 women) healthy nonsmokers aged 18 to 80 years were analyzed. Age and height were found to be the major determinants of FEV1 and FVC, with a linear decline of height-adjusted values with age in both sexes. Spirometric values of this population have increased compared to Chinese populations of similar sex, age, and height two decades ago. Reference values derived from white populations were higher than our values by 5 to 19%, and the degree of overestimation varied with age, sex, and lung function parameter. We also demonstrated that the blanket application of correction factors for Asian populations may not be appropriate. In this study cohort, the distribution-free estimation of age-related centiles was more appropriate for the determination of lower limits of normal. CONCLUSIONS: Our findings underscore the need to use reference values based on updated data derived from local populations or those matched for ethnicity and other sociodemographic characteristics.

Altered exercise gas exchange as related to microalbuminuria in type 2 diabetic patients.

STUDY OBJECTIVE: Microalbuminuria in diabetes mellitus is a risk factor for cardiovascular disease. We hypothesized that microalbuminuria in type 2 diabetic patients is related to impaired cardiopulmonary function during exercise, and that the severity of impairment is correlated with the degree of microalbuminuria. DESIGN: Twenty of each of the following categories of subjects performed symptom-limited cardiopulmonary exercise testing on a cycle ergometer: (1) type 2 diabetic patients with normoalbuminuria (daily urinary albumin excretion [UAE] < 30 mg/d); (2) type 2 diabetic patients with microalbuminuria (daily UAE, 30 to 300 mg/d); and (3) normal control subjects. MEASUREMENTS AND RESULTS: Oxygen consumption (VO(2)) of patients with microalbuminuria was lower than that of control subjects at anaerobic threshold (AT) [p < 0.001], and was lower than both control subjects (p < 0.001) and patients with normoalbuminuria (p = 0.015) at peak exercise. There was a progressive worsening in gas exchange efficiency at the lungs, as measured by minute ventilation (VE)/carbon dioxide production (VCO(2)) at AT or DeltaVE/DeltaVCO(2) slope, (p = 0.006 and p = 0.019, respectively) going from control subjects to patients with normoalbuminuria and then to patients with microalbuminuria. Left ventricular ejection fractions and BP were similar in patients with normoalbuminuria and microalbuminuria. More patients with microalbuminuria (n = 9) than with normoalbuminuria (n = 2) demonstrated diastolic dysfunction (p = 0.013). These 11 patients had lower peak VO(2) values (p = 0.001) and higher daily UAE (p = 0.028). An inverse linear relationship was found between peak VO(2) and log(10) daily UAE (r = - 0.57, r(2) = 0.29, p < 0.001). CONCLUSIONS: Abnormalities reflecting reduced oxygen transport and impaired gas exchange efficiency were found during exercise, and were especially profound in patients with microalbuminuria. These changes could be secondary to pulmonary microangiopathy and myocardial interstitial changes. Increases in capillary permeability to proteins may take place in the myocardium as they do in the kidneys, and contribute to impaired myocardial distensibility and hence diastolic dysfunction.

Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS).

Severe acute respiratory syndrome (SARS) is frequently complicated with acute respiratory failure. In this article, we aim to focus on the management of the subgroup of SARS patients who are critically ill. Most SARS patients would require high flow oxygen supplementation, 20-30% required intensive care unit (ICU) or high dependency care, and 13-26% developed acute respiratory distress syndrome (ARDS). In some of these patients, the clinical course can progress relentlessly to septic shock and/or multiple organ dysfunction syndrome (MODS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). Superimposed bacterial and other opportunistic infections are common, especially in those treated with mechanical ventilation. Subcutaneous emphysema, pneumothoraces and pneumomediastinum may arise spontaneously or as a result of positive ventilatory assistance. Older age is a consistently a poor prognostic factor. Appropriate use of personal protection equipment and adherence to infection control measures is mandatory for effective infection control. Much of the knowledge about the clinical aspects of SARS is based on retrospective observational data and randomized-controlled trials are required for confirmation. Physicians and scientists all over the world should collaborate to study this condition which may potentially threaten human existence.

Over 8 years experience on severe acute poisoning requiring intensive care in Hong Kong, China.

In order to obtain up-to-date information on the pattern of severe acute poisoning and the characteristics and outcomes of these patients, 265 consecutive patients admitted to an intensive care unit in Hong Kong for acute poisoning from January 2000 to May 2008 were studied retrospectively. Benzodiazepine (25.3%), alcohol (23%), tricyclic antidepressant (17.4%), and carbon monoxide (15.1%) were the four commonest poisons encountered. Impaired consciousness was common and intubation was required in 67.9% of admissions, with a median duration of mechanical ventilation of less than 1 day. The overall mortality was 3.0%. Among the 257 survivors, the median lengths of stay in the intensive care unit and acute hospital (excluding days spent in psychiatric ward and convalescent hospital) were less than 1 day and 3 days, respectively. Factors associated with a longer length of stay included age of 65 or older, presence of comorbidity, Acute Physiology and Chronic Health Evaluation II score of 25 or greater, and development of shock, rhabdomyolysis, and aspiration pneumonia, while alcohol intoxication was associated with a shorter stay. This is the largest study of its kind in the Chinese population and provided information on the pattern of severe acute poisoning requiring intensive care admission and the outcomes of the patients concerned.

Corticosteroid treatment of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: The patterns of corticosteroids usage in severe acute respiratory syndrome (SARS) and associated treatment outcomes in Hong Kong were studied. METHOD: Patients> or =18 years old who either had not received corticosteroid or had taken corticosteroids within 14 days from symptom onset were included. Patients receiving corticosteroids beyond 15 days or other investigational treatment within 21 days from symptom onset were excluded. Of 1313 eligible patients, 1287 with major corticosteroid dosage-type combinations were analysed. RESULTS: Crude death rate was lower among 1188 steroid-treated patients compared to 99 patients in Group No Steroid (17.0% vs. 28.3%). Among four corticosteroid groups studied, mortality was lowest in the low-dose oral prednisolone (Group P) and high-dose methylprednisolone (Group MP) groups. On multivariate analysis of the corticosteroid groups, independent factors related to death were: corticosteroid group, older age, co-morbidity, worse chest X-ray score, worse respiratory status at Days 8-10 and higher admission white cell count. Again Groups P and MP had significantly lower adjusted odds ratios for death and lower bacterial and fungal culture rates. Despite worse chest X-ray scores and higher cumulative corticosteroid dosages in Group MP compared to Group P, fewer patients required rescue pulsed corticosteroid. Patients on hydrocortisone (Group HC) had the highest positive culture rates. CONCLUSION: We speculate that corticosteroid with higher in-vitro inflammatory potency administered at timing and dosages commensurate with disease severity may be conducive to better outcome from SARS as a consequence of more effective control of immunopathological lung damage.

Outcome of coronavirus-associated severe acute respiratory syndrome using a standard treatment protocol.

OBJECTIVE: There is so far no consensus on the optimal treatment strategy for the coronavirus-associated severe acute respiratory syndrome (SARS). We aimed to analyse the outcomes of a standard treatment strategy comprising antibiotics, a combination of ribavirin, a 3-week step-down course of corticosteroids, and the possibility of pulsed methylprednisolone rescue in the event of deterioration. METHODOLOGY: This was a prospective cohort study performed at a major public-funded hospital in Hong Kong. Eighty-eight World Health Organisation/Centers for Disease Control and Prevention probable cases of SARS (97% laboratory-confirmed) were treated with a standard protocol previously reported. Seventy-one patients treated de novo were analysed in detail with regard to time to clinical stabilization after combination treatment, requirement of additional therapy (pulsed methylprednisolone; assisted ventilation); and final outcomes (recovery, mortality). RESULTS: The mean age was 42. Twenty-one patients (24%) had comorbidities. Three of 71 treated de novo recovered with antibiotics alone. The remaining 68 received combination treatment at a mean of 5.8 days after symptom onset, of whom 30 subsequently required pulsed methylprednisolone rescue (independent predictors: older age and higher LDH) and 18 required assisted ventilation (independent predictors: older age, higher oxygen requirement and creatinine level). Their median time to clinical stabilization was 8.0 days after combination treatment (independent predictor for longer time to stabilization: median age of 41 or above). Common complications were hyperglycaemia (58%), pneumo-mediastinum/thoraces (13%), psychiatric manifestations (7%) and ventilator-associated pneumonia (2%). One patient (1%) died of SARS-related respiratory failure. All-cause mortality was 3.4%, occurring in patients aged > 65 years only. None of the discharged survivors required continuation of oxygen therapy. CONCLUSIONS: This standard treatment protocol resulted in overall satisfactory outcomes. Randomized controlled trial is suggested to confirm its efficacy.