C-reactive protein to rule out complicated pneumococcal disease manifestations: a retrospective cohort study in adults with pneumococcal bacteraemia.

OBJECTIVES: To explore the negative predictive value (NPV) of C-reactive protein (CRP) at admission to exclude complicated disease manifestations of pneumococcal disease. METHODS: A Dutch multicentre retrospective cohort study was conducted between 01-01-2012 and 30-06-2020. Adults with positive blood cultures for Streptococcus pneumoniae, whose CRP was measured at admission and whose infection focus was known, were included. Electronic medical and microbiological records were reviewed. RESULTS: Of the 832 bacteraemic patients enrolled, 30% had complicated manifestations of pneumococcal disease; most frequent were pleural effusion (8.9%), pleural empyema (5.4%) and meningitis (7.5%). Compared to solitary pneumonia, patients with pleural effusion and empyema presented with higher CRP levels. Although low CRP levels did not exclude complicated disease in general, a CRP level < 114 mg/L at admission could reliably exclude empyema among adult pneumonia patients with an NPV of 93% and a specificity of 26%. However, in cases where pleural fluid was present, CRP levels were mostly > 114 mg/L, such that suspicion of empyema could only be ruled out in a minority of cases (10%). CONCLUSIONS: Complicated manifestations are prevalent in adult pneumococcal bacteraemia. Low blood CRP levels can reliably exclude the development of pulmonary empyema. Practical value may be largest in settings without thoracic imaging at hand.

Should the diagnosis of COPD be based on a single spirometry test?

Clinical guidelines indicate that a chronic obstructive pulmonary disease (COPD) diagnosis is made from a single spirometry test. However, long-term stability of diagnosis based on forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) ratio has not been reported. In primary care subjects at risk for COPD, we investigated shifts in diagnostic category (obstructed/non-obstructed). The data were from symptomatic 40+ years (ex-)smokers referred for diagnostic spirometry, with three spirometry tests, each 12±2 months apart. The obstruction was based on post-bronchodilator FEV1/FVC < lower limit of normal (LLN) and <0.70 (fixed ratio). A total of 2,352 subjects (54% male, post-bronchodilator FEV1 76.5% predicted) were studied. By LLN definition, 32.2% were obstructed at baseline, but 32.2% of them were no longer obstructed at years 1 and/or 2. By fixed ratio, these figures were 46.6 and 23.8%, respectively. Overall, 14.3% of subjects changed diagnostic category by 1 year and 15.4% by 2 years when applying the LLN cut-off, and 15.1 and 14.6% by fixed ratio. Change from obstructed to non-obstructed was more likely for patients with higher body mass index (BMI) and baseline short-acting bronchodilator (SABA) users, and less likely for older subjects, those with lower FEV1% predicted, baseline inhaled steroid users, and current smokers or SABA users at year 1. Change from non-obstructed to obstructed was more likely for males, older subjects, current smokers and patients with lower baseline FEV1% predicted, and less likely for those with higher baseline BMI. Up to one-third of symptomatic (ex-)smokers with baseline obstruction on diagnostic spirometry had shifted to non-obstructed when routinely re-tested after 1 or 2 years. Given the implications for patients and health systems of a diagnosis of COPD, it should not be based on a single spirometry test.

COPD prognosis in relation to diagnostic criteria for airflow obstruction in smokers.

The aim of this study was to establish which cut-off point for the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e. fixed 0.70 or lower limit of normal (LLN) cut-off point) best predicts accelerated lung function decline and exacerbations in middle-aged smokers. We performed secondary analyses on the Lung Health Study dataset. 4045 smokers aged 35-60 years with mild-to-moderate obstructive pulmonary disease were subdivided into categories based on presence or absence of obstruction according to both FEV1/FVC cut-off points. Post-bronchodilator FEV1 decline served as the primary outcome to compare subjects between the categories. 583 (14.4%) subjects were nonobstructed and 3230 (79.8%) subjects were obstructed according to both FEV1/FVC cut-off points. 173 (4.3%) subjects were obstructed according to the fixed cut-off point, but not according to the LLN cut-off point ("discordant" subjects). Mean±SE post-bronchodilator FEV1 decline was 41.8±2.0 mL·year(-1) in nonobstructed subjects, 43.8±3.8 mL·year(-1) in discordant subjects and 53.5±0.9 mL·year(-1) in obstructed subjects (p<0.001). Our study showed that FEV1 decline in subjects deemed obstructed according to a fixed criterion (FEV1/FVC <0.70), but non-obstructed by a sex- and age-specific criterion (LLN) closely resembles FEV1 decline in subjects designated as non-obstructed by both criteria. Sex and age should be taken into account when assessing airflow obstruction in middle-aged smokers.