Impact of Inhaled Corticosteroid Use on Elderly Chronic Pulmonary Disease Patients with Community Acquired Pneumonia
Community-acquired pneumonia (CAP) and chronic obstructive pulmonary disease (COPD) are significant health concerns, particularly in the aging global population. The use of inhaled corticosteroids (ICS), a cornerstone treatment for asthma, COPD with frequent acute exacerbations, and asthma-COPD overlap (ACO), has been associated with changes in the local lung microbiome and abnormal lung immunity, potentially increasing the risk of pneumonia. However, the impact of ICS use on CAP mortality remains controversial. This multicenter, retrospective study aimed to explore the association between ICS use during hospitalization and short-term mortality in elderly patients with CAP and chronic pulmonary disease (CPD).
The study was conducted on hospitalized patients aged 65 years and older with CAP from the CAP-China network between January 1, 2014, and December 31, 2014. The study was approved by the Human Subject Protection Program Institutional Review Board of China-Japan Friendship Hospital and local institutional review boards of participating hospitals. Patient consent was waived due to the retrospective and observational nature of the study. The study was registered on ClinicalTrials.gov under the number NCT02489578.
CPD was defined as the presence of asthma, COPD, or ACO. ACO was characterized by persistent airflow limitation with features typically associated with both asthma and COPD. ICS exposure was defined as the use of fluticasone, budesonide, or beclomethasone alone or in combination with β-receptor agonists and/or adrenergic receptor blockers through dry powder inhalers, atomized inhalation metered-dose inhalers, or aerosol inhalation during hospitalization.
The study enrolled 2437 patients with CAP aged 65 years and older. Among them, 1997 (81.9%) were classified as without CPD, 355 (14.6%) as COPD, 64 (2.6%) as asthma, and 21 (0.9%) as ACO. The mean age of asthmatic patients with CAP was significantly lower than that of patients in the COPD or without CPD groups. The male proportion was also significantly lower in the asthma group compared to the COPD and without CPD groups. The proportion of patients using ICS during hospitalization was significantly lower in patients without CPD than in those with CPD. No significant differences were identified in pneumonia severity index scores, clinical stability on admission, intensive care unit (ICU) admission, mechanical ventilation, treatment failure, in-hospital mortality, 30-day mortality, or length of stay among the four groups.
After propensity score matching (PSM), 384 pairs of older patients were included in the multivariate logistic analysis of 30-day mortality. Blood sodium level 10 × 10^9/L, and the CURB-65 (confusion, uremia >7 mmol/L, respiratory rate ≥30/minutes, hypotension, and aged 65 years or older) score were independent risk factors for 30-day mortality, whereas the use of ICS during hospitalization was a protective factor. The Kaplan-Meier (KM) curve demonstrated that older patients who used ICS during hospitalization in the matched cohort had significantly higher survival.
For the subgroup of patients with COPD (n = 376), the CURB-65 score, blood sodium level <130 mmol/L, and arterial oxygen saturation <90% were independent risk factors for 30-day mortality, whereas the use of ICS during hospitalization was not a protective factor. However, the KM curve indicated that the use of ICS during hospitalization significantly reduced the 30-day mortality in the subgroup of patients with COPD.
The study aimed to evaluate the association between the use of ICS during hospitalization and short-term mortality in older CAP patients and those with CPD in China. It found that hyponatremia, leukocytosis, and the CURB-65 score were independent risk factors associated with 30-day mortality in matched 384 pairs of patients, whereas the use of ICS during hospitalization was a protective factor. The use of ICS during hospitalization in patients with COPD significantly decreased short-term mortality, but it was not an independent risk factor.
A meta-analysis of the effect of COPD on mortality in patients with CAP showed no associations between the presence of COPD and in-hospital or 30-day mortality in CAP patients. A prospective study on 4079 patients with CAP over a 12-year period identified no significant differences in ICU admission, mechanical ventilation, and 30-day mortality among patients with or without asthma, consistent with the results of this study. The mortality rate of patients with CAP and ACO was low in this study.
The role of corticosteroids against the inflammatory response to infection in patients with CAP is debatable. Patients with severe CAP may benefit from systemic corticosteroids. Some patients with CAP, even those without CPD, may experience wheezing, chest tightness, severe and frequent cough due to airway hyper-responsiveness, and airway mucus hypersecretion. Aerosol inhalation of ICS alone or combined with β-receptor agonists and/or M-cholinergic receptor blockers may be appropriate for such patients. In this study, approximately one-third of the patients without CPD experienced wheezing or chest tightness, and 11.2% of these patients were prescribed ICS during hospitalization. The proportion of ICS use was 33.3%–37.5% in patients with CPD. The KM curves in the current study indicate that the use of ICS during hospitalization significantly reduces 30-day mortality in the matched cohort and patients with COPD. The use of ICS during hospitalization was a protective factor in the matched cohort but not in patients with COPD. A study analyzing the association of ICS exposure with mortality in 6353 older patients with CAP and COPD showed that prehospital use of ICS was significantly associated with lower 30-day mortality, and the KM curve indicated that patients with ICS use had significantly higher survival over the first 90 days after admission. Another study confirmed that the use of ICS decreased 30-day mortality in patients with CAP and COPD, generally concordant with the data from this study.
In the present study, hyponatremia, leukocytosis, and the CURB-65 score were independent risk factors for short-term mortality in older patients with CAP, consistent with previous observations. The incidence of hyponatremia was 8%–31% in adult patients with CAP and was associated with increased mortality, more severe pulmonary inflammation with higher levels of leukocytes and C-reactive protein, more severe disease severity, more frequent ICU admission, and prolonged hospital stay. In patients with CAP and COPD, dyspnea occurred in 60.4% of cases. Data showed hypoxemia was associated with 30-day mortality in such a population, consistent with the report from the Pneumonia Patient Outcomes Research Team cohort study.
The present study had several limitations. First, data regarding prehospitalization use of ICS, ICS dose, duration of treatment, and combination with long-acting β-agonists and/or M-cholinergic receptor blockers were not systematically documented. Second, the diagnoses of COPD and asthma were self-reported, and data on lung function related to CPD were lacking. Therefore, the relationship between ICS and/or bronchodilators, lung function, and mortality could not be evaluated. Third, some bias may have been introduced owing to the partial loss of laboratory data when performing the statistical analysis.
In conclusion, this study revealed that the use of ICS during hospitalization was associated with a significantly lower 30-day mortality in older patients with CAP. These findings provide new perspectives on the potential benefit of ICS use as an immunomodulatory therapy in older patients with CAP. Therefore, further multicenter prospective studies are warranted.
doi.org/10.1097/CM9.0000000000002936
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