Predicting Pneumonia in Chronic Obstructive Pulmonary Disease. Have We Unraveled the Network of Risks?

Abstract

Have We Unraveled the Network of Risks? Inhaled corticosteroids (ICS) reduce exacerbation rates in patients with chronic obstructive pulmonary disease (COPD) but may also cause adverse effects, including pneumonia (1, 2). Blood eosinophil counts can predict the clinical response to ICS and ,100 eosinophils/ml is associated with a low probability of a reduction in exacerbation rates (3). Based in part on these data, the use of ICS in clinical practice is becoming more personalized, weighing the possibility of benefit (using exacerbation history and blood eosinophil counts) against the risk of adverse events, including pneumonia (4, 5). In this issue of the Journal, Martinez-Garcia and colleagues (pp. 1078-1085) report the relationships between pneumonia risk and ICS use, blood eosinophil counts, and chronic bacterial infection (CBI) of the airways (assessed using sputum samples) from a cohort of 201 patients with COPD followed for a median of 84 months (6). Previous studies have shown that pneumonia risk factors in COPD include ICS use, older age, lower FEV 1 , lower body mass index, and previous pneumonia (7-9). An important novel aspect of this study is that bacterial infection data is included in the analysis of pneumonia risk. Bacterial isolates were detected in 42.3% of patients on at least one occasion, whereas CBI was present in 22.4%. Univariate analysis showed that older age, lower FEV 1 , presence of bronchiectasis, exacerbation rates, and ,100 eosinophils/ml were associated with CBI. These risk factors were also associated with pneumonia risk, as was CBI and ICS treatment. A multivariate Cox proportional hazard regression model showed that age, FEV 1 , CBI, and ,100 eosinophils/ml were all independently associated with pneumonia. Of note, ICS use itself was not associated with pneumonia in the overall population, although ICS further increased the risk of pneumonia in those with CBI and ,100 eosinophils/ml. Few studies of pneumonia in COPD have included blood eosinophil counts as a risk factor, mostly showing either a weak or no association (3, 10). Martinez-Garcia and colleagues also found that higher eosinophil thresholds (e.g., ,150 or ,300 cells/ml) were not associated with pneumonia risk, but very low eosinophil counts (,100 cells/ml) were associated with pneumonia, and this was the most important risk factor in the adjusted Cox regression model, ahead of age and FEV 1 (6). This is an observational study, in contrast to previous analyses of eosinophils and pneumonia risk that were based on data from randomized controlled trials (RCTs) (3, 10), and differences in study design or population characteristics may explain the varying results. Also, the way that pneumonia was defined varied, and even when chest radiographs

The relationship between airway immunoglobulin activity and eosinophils in COPD

“…Lower airway eosinophil numbers are associated with increased presence of colonizing bacteria in stable COPD patients, and ICS use was associated with an increase in bacterial load only in patients with lower eosinophils 6‐9 . Overall, these previous findings suggest that COPD patients with lower eosinophil counts have a different susceptibility to bacterial infection 22 . Our data showing lower immunoglobulin levels and activity in COPD eosinophil low patients provide a potential mechanistic explanation for these observations.…”

“…[6][7][8][9] Overall, these previous findings suggest that COPD patients with lower eosinophil counts have a different susceptibility to bacterial infection. 22 Our data showing lower immunoglobulin levels and activity in COPD eosinophil low patients provide a potential mechanistic explanation for these observations. The risk of pneumonia in COPD patients is associated with certain clinical characteristics, such as previous pneumonia events, age and lower body mass index.…”

Pharmacological treatment of stable chronic obstructive pulmonary disease

“…50 Overall, these findings implicate interactions between eosinophilic inflammation and the microbiome that influence ICS response. 51,52 Multiple studies have demonstrated statistically significant associations between blood and lung eosinophil counts, but the strength of the relationship has been weak to moderate. 8 Technical issues such as the quality of sputum slides can negatively impact this relationship.…”

Using Blood Eosinophil Count as a Biomarker to Guide Corticosteroid Treatment for Chronic Obstructive Pulmonary Disease

“…Sometimes blood eosinophils also have been shown to have a protective effect in COPD. Higher blood eosinophils have been associated with fewer infections and possibly a better survival, but the mechanisms to explain these findings have not been defined [ 40 , 62 , 63 , 64 , 65 , 66 , 67 ].…”