Patients With COPD, PRISm at Increased All-Cause, Cause-Specific Mortality Risk

Patients with chronic obstructive pulmonary disease (COPD) and/or preserved ratio impaired spirometry (PRISm) had an increased risk of all-cause and cause-specific mortality, according to a study published in Respiratory Research.¹

Traditionally, a clinical COPD diagnosis requires patients to have a spirometry FEV₁/FVC ratio of less than 0.7; FEV₁/FVC is the maximum amount of air that a patient can forcibly expel during the first second following maximal inhalation (FEV₁) divided by the forced vital capacity (FVC). However, the study authors noted that patients not meeting this diagnosis may still experience lung obstruction abnormalities.

The researchers explained that PRISm has been proposed as preclinical COPD abnormal spirometry; patients are diagnosed with PRISm if they have an FEV₁/FVC ratio greater or equal to 0.7 and an FEV₁ less than 0.8. The diagnosis is associated with poor health outcomes, including increased cardiovascular mortality, higher body mass index (BMI), and respiratory symptoms. Consequently, those with PRISm are not easily categorized into a specific disease pathway, meaning the causal pathway of PRISm and COPD remains unclear.

Since COPD directly costs the US health care system $32 billion annually,² the researchers explained that it is important to better understand the related mortality risks and prevalence associated with abnormal spirometry levels.¹ Consequently, they conducted a study to estimate the prevalence, all-cause mortality risk, and cause-specific mortality risk of PRISm and COPD in the US adult population. To do so, they used spirometry data collected during 3 waves (2007-2008, 2009-2010, and 2011-2012) of the National Health and Nutrition Examination Survey (NHANES), “a nationally representative, cross-sectional survey of the civilian, noninstitutionalized US population.”³

Female patient experiencing breathing difficulties | Image Credit: RFBSIP - stock.adobe.com

The researchers estimated PRISm and COPD prevalence using a subset of US adults aged 20 to 79 years eligible for spirometry tests. The final sample for the prevalence analysis (n = 13,328) consisted of those with complete spirometry values and covariate data. Similarly, the final sample for the mortality analyses (n = 13,307) included those who met the prevalence analysis inclusion criteria and had their vital status confirmed through the NHANES Linked Mortality Files. After diagnosing the included patients with COPD or PRISm, those with COPD were further classified into Global Initiative for Obstructive Lung Disease (GOLD) stages based on predicted FEV₁ values: GOLD 1 (FEV₁ ≥ 80%), GOLD 2 (50 < FEV₁ < 80%), and GOLD 3 + 4 (FEV₁ ≤ 50%).

PRISm was prevalent in 9.8% (95% CI, 12.8%-14.9%) of the study population, while COPD was prevalent in 13.8% (95% CI, 8.9%-10.8%). Overall, rate of COPD was higher in male patients (range, 17.4%-17.9%) and PRISm was higher among female patients (range, 10.5%-11.3%). In terms of age, COPD prevalence was highest among patients aged 65 to 79 years (range, 28.1%-36.1%). However, PRISm prevalence was highest among patients aged 40 to 64 years (range, 11.0%-11.9%). As for race/ethnicity, PRISm was most prevalent among non-Hispanic Black patients (range, 31.4%-37.4%), while COPD was most prevalent among non-Hispanic White patients (range, 15.5%-17.5%).

Compared with never users, the researchers found COPD prevalence to be higher among current and former cigarette users. Lastly, COPD prevalence was lower for those with obesity than those with a BMI categorized as overweight or normal. Conversely, overall PRISm estimates were higher for patients with obesity than those with a normal BMI.

As for the mortality analyses, the researchers determined that 1079 patients in the final sample died (8.15%), with a median follow-up of 9.4 years. In multivariable-adjusted models, all-cause mortality risk was higher among patients at GOLD 2 stage (HR, 2.1; 95% CI, 1.7-2.6) or higher (HR, 4.2; 95% CI, 2.7-6.5); it was also higher among those with PRISm (HR, 2.3; 95% CI, 1.9-2.9).

Additionally, the researchers considered COPD and PRISm as significant predictors of cause-specific mortality. More specifically, they associated those with GOLD 2 stage disease (HR, 2.0; 95% CI, 1.4-2.8) or PRISm (HR, 2.0; 95% CI, 1.2-3.2) with significant cancer mortality risk. Also, those with GOLD 3 + 4 stage disease (HR, 4.7; 95% CI, 2.3-9.8) showed the highest cardiovascular mortality risk, followed by GOLD 2 (HR, 2.4; 95% CI, 1.6-3.7) and PRISm (HR, 2.4; 95% CI, 1.6-3.6). Lastly, they associated both patients with PRISm (HR, 5.3; 95% CI, 1.1-26.0) and GOLD 3 + 4 (HR, 53.2; 95% CI, 14.0-202.0) with an increased chronic lower respiratory disease-related mortality risk.

The researchers acknowledged their study's limitations, one being that the NHANES only had spirometry data available from between 2007 and 2012 because it discontinued spirometry examination in 2013; this limited their ability to examine both longer-term and more recent trends in PRISm and COPD prevalence. Also, overall, spirometry data are rarely collected in US population-based studies, making examinations of PRISm and COPD challenging. Therefore, they noted that collecting longitudinal spirometric data would enhance future research.

“Much remains unknown about PRISm and the extent to which it may progress to a formal COPD diagnosis; as such, increasing spirometric data collection is essential,” the authors concluded.

References

1. Cadham CJ, Oh H, Han MK, et al. The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007-2012. Respir Res. 2024;25(1):208. doi:10.1186/s12931-024-02841-y
2. Løkke A, Lange P, Lykkegaard J, et al. Economic burden of COPD by disease severity - a nationwide cohort study in Denmark. Int J Chron Obstruct Pulmon Dis. 2021;16:603-613. doi:10.2147/COPD.S295388
3. NHANES - National Health and Nutrition Examination Survey Homepage. CDC. Published 2019. Accessed May 20, 2024. https://www.cdc.gov/nchs/nhanes/index.htm