Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.

BackgroundPrediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease.AimTo determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations.MethodsThis was a 2-year prospective cohort study of COPD patients. Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared.ResultsAmong 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002). For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001). Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation.ConclusionIn this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices.

Objective Although chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, the association between the neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) and the clinical status of COPD has not been well studied. We hypothesized that the NLR is associated with disease severity and exacerbation in COPD patients. Methods We performed blood testing, pulmonary function testing, chest computed tomography, a body composition analysis, and a 6-minute walk test and applied the modified Medical Research Council (MMRC) dyspnea scale for 141 stable COPD patients. In addition, we calculated the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index to evaluate the disease severity. Finally, we examined the association between the NLR and clinical parameters in stable COPD patients, and we further investigated changes in the NLR between exacerbation and the stable state. Results The NLR was positively correlated with the BODE index, extent of emphysema, and MMRC score (p<0.001 for all), while inversely correlated with airflow obstruction (p<0.001), body mass index (p<0.001), fat-free mass index (p=0.001), and the 6-minute walk distance (p<0.001). We obtained the NLR during exacerbation from 49 patients. The NLR was significantly higher at exacerbation compared to the stable state (p< 0.001). Conclusion The NLR was associated with disease severity and exacerbation in COPD patients. Therefore, the usefulness of the NLR in COPD patients should be elucidated in clinical settings in future investigations.

PurposeThis study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD.Patients and methodsA total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II–IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa. The primary endpoint was inspiratory capacity (IC) at peak post-dose.ResultsAdjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001). Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001). Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254). In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337).ConclusionTiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients. A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol.

Integrated education for older patients with chronic obstructive pulmonary disease effectively improved patients' information needs, activities of daily living, dyspnea score, BODE index and reduced hospitalizations during the observed period. Geriatr Gerontol Int 2011; 11: 422-430.