Background: Lung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remain unclear. There is growing interest in the role of granzyme B (GzmB) because CD8+ T cells can induce apoptosis of target cells by releasing GzmB, which in turn may cause tissue injury and remodeling. However, GzmB is also expressed by regulatory cells, which are able to suppress CD8+ T cell. The role of GzmB+ cells needs to be defined in COPD. Methods: GzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 nonsmoking control, 12 panlobular emphysema (PLE) and 30 centrilobular emphysema (CLE) subjects were localized by immunohistochemical method. Positively stained cells on alveolar wall were counted and length of corresponding alveolar wall was measured. The results were expressed as mean number of positively stained cells per mm of alveolar wall in each subject. Results: The number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05 and p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and forced expiratory volume in 1 second (FEV1) (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1. Conclusion Our finding that number of alveolar GzmB+ cells was associated with FEV1 suggests that GzmB+ cells might have protective role in the progression of lung destruction and airflow limitation in CLE, which is the predominant emphysema subtype of COPD.

Background: Lung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remain unclear. There is growing interest in the role of granzyme B (GzmB) because CD8+ T cells can induce apoptosis of target cells by releasing GzmB, which in turn may cause tissue injury and remodeling. However, GzmB is also expressed by regulatory cells, which are able to suppress CD8+ T cell. The role of GzmB+ cells needs to be defined in COPD. Methods: GzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 nonsmoking control, 12 panlobular emphysema (PLE) and 30 centrilobular emphysema (CLE) subjects were localized by immunohistochemical method. Positively stained cells on alveolar wall were counted and length of corresponding alveolar wall was measured. The results were expressed as mean number of positively stained cells per mm of alveolar wall in each subject. Results: The number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05 and p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and forced expiratory volume in 1 second (FEV1) (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1. Conclusion Our finding that number of alveolar GzmB+ cells was associated with FEV1 suggests that GzmB+ cells might have protective role in the progression of lung destruction and airflow limitation in CLE, which is the predominant emphysema subtype of COPD.

INTRODUCTIONPneumonia is associated with considerable mortality. However, there is limited information on age-specific prognostic factors for death from pneumonia.

METHODSPatients hospitalised with a diagnosis of pneumonia through the emergency department were stratified into three age groups: 18-64 years, 65-84 years and ≥ 85 years. Multivariate logistic regression and receiver operating characteristic curve analyses were conducted to evaluate prognostic factors for mortality and the performance of pneumonia severity scoring tools for mortality prediction.

RESULTSA total of 1,902 patients were enrolled (18-64 years: 614 [32.3%]; 65-84 years: 944 [49.6%]; ≥ 85 years: 344 [18.1%]). Mortality rates increased with age (18-64 years: 7.3%; 65-84 years: 16.1%; ≥ 85 years: 29.7%; p < 0.001). Malignancy and tachycardia were prognostic of mortality among patients aged 18-64 years. Male gender, malignancy, congestive heart failure and eight other parameters reflecting acute disease severity were associated with mortality among patients aged 65-84 years. For patients aged ≥ 85 years, altered mental status, tachycardia, blood urea nitrogen, hypoxaemia, arterial pH and pleural effusion were significantly predictive of mortality. The Pneumonia Severity Index (PSI) was more sensitive than CURB-65 (confusion, uraemia, respiratory rate ≥ 30 per minute, low blood pressure, age ≥ 65 years) for mortality prediction across all age groups.

CONCLUSIONThe predictive effect of prognostic factors for mortality varied among patients with pneumonia from the different age groups. PSI performed significantly better than CURB-65 for mortality prediction, but its discriminative power decreased with advancing age.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Algorithms ; Community-Acquired Infections ; diagnosis ; mortality ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Patient Admission ; Pneumonia ; diagnosis ; mortality ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Risk Factors ; Sensitivity and Specificity ; Severity of Illness Index ; Singapore ; epidemiology ; Young Adult