Lower Respiratory Infections Pre-COPD May Increase Exacerbation, Mortality Risk

Patients with COPD who had LRTIs prior to their COPD diagnosis were more likely to have future exacerbations.

An increasing frequency and severity of lower respiratory tract infections (LRTIs) before a diagnosis of chronic obstructive pulmonary disease (COPD) is associated with an increased rate of future COPD exacerbations and mortality risk after COPD diagnosis, according to a study in Thorax.

Investigators in the United Kingdom sought to explore the link between LRTIs prior to COPD diagnosis and future exacerbations and mortality through the exacerbations of COPD and their Outcomes (EXACOS-UK) study, an observational study using data from the Clinical Practice Research Datalink (CPRD) Aurum and Office for National Statistics (ONS). Participants were least 40 years of age, currently or previously smoked, and had data recorded in CPRD Aurum from January 1, 2004, onward, that included 1 year of data prior to their COPD diagnosis. Study outcomes were postdiagnosis exacerbations of COPD and mortality.

A total of 215,234 patients (mean [SD] age, 66.9 [11.4] years; 53.3% male) with newly diagnosed COPD were included. At baseline, 158,074 (73.4%) patients had no LRTIs, 18,081 (8.4%) had 1 mild LRTI, 6133 (2.8%) had at least 2 mild LRTIs, 19,787 (9.2%) had 1 moderate LRTI, 6227 (2.9%) had at least 2 moderate LRTIs, and 6932 (3.2%) had at least 1 severe LRTIs requiring hospitalization.

After a median follow-up of 4.4 years (interquartile range [IQR], 1.9-7.9), 948,576 COPD exacerbation events were recorded. Patients who had 1 moderate LRTI or at least 2 moderate LRTIs had a higher incidence rate of future COPD exacerbations of any severity vs patients with no LRTI in the year before COPD diagnosis (adjusted incidence rate ratio [aIRR], 1.81; 95% CI, 1.78-1.85; and aIRR, 2.55; 95% CI, 2.48-2.63, respectively). Patients with severe LRTIs at baseline also had a higher incidence rate but with a smaller magnitude of association (adjusted IRR, 1.75; 95% CI, 1.70-1.80). Participants who had 1 or at least 2 mild LRTIs had an increased incidence rate vs those with no LRTIs but to a lower extent (adjusted IRR, 1.16; 95% CI, 1.14-1.18 and adjusted IRR, 1.51; 95% CI, 1.46-1.55, respectively).

Overall, this study suggests that LRTIs prior to COPD diagnosis may be indicative of subsequent increased rate of exacerbations and increased risk of mortality and should be taken seriously by health care professionals

The association pattern was similar for future moderate exacerbations of COPD, and the strongest association occurred between baseline severe LRTIs and future severe exacerbations (adjusted IRR, 3.02; 95% CI, 2.87-3.18).

During the follow-up, 51,669 (24%) patients with COPD died, with the highest risk occurring in the baseline severe LRTI group (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.84-1.99), followed by those with at least 2 moderate and 1 moderate baseline LRTI (aIRR, 1.22; 95% CI, 1.17-1.27; and aIRR, 1.10; 95% CI, 1.07-1.13, respectively). An association between 1 or at least 2 mild baseline LRTIs was observed but to a lesser extent (aHR, 1.11; 95% CI, 1.07-1.15, and aHR, 1.14; 95% CI, 1.08-1.22, respectively).

The strongest association of COPD and CVD-related mortality occurred in patients with at least 1 severe LRTI, compared with those with no baseline LRTIs (adjusted HR, 2.32; 95% CI, 2.15-2.50 and IRR, 1.68; 95% CI, 1.55-1.82, respectively).

In a sensitivity analysis that grouped baseline LRTI events into no LRTI, 1 primary care-recorded LRTI, 2 primary care-recorded LRTIs, at least 3 primary care-recorded LRTIs, and at least 1 hospitalized LRTI, all categories were significantly associated with future COPD exacerbations vs no baseline LRTIs.

Among several study limitations, some hospitalized events may not have been severe events clinically. Also, LRTI events were included as LRTI/pneumonia recorded events with or without antibiotic prescriptions, and it is possible that events could have been missed if they were coded as COPD exacerbations. Furthermore, residual confounding is likely, and the results do not imply causation.

“Overall, this study suggests that LRTIs prior to COPD diagnosis may be indicative of subsequent increased rate of exacerbations and increased risk of mortality and should be taken seriously by health care professionals,” stated the investigators.

Disclosure: This study was funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Whittaker H, Nordon C, Rubino A, et al. Frequency and severity of respiratory infections prior to COPD diagnosis and risk of subsequent postdiagnosis COPD exacerbations and mortality: EXACOS-UK health care data study. Thorax. Published online October 31, 2022. doi:10.1136/thorax-2022-219039