The global significance of PRISm: how data from low- and middle-income countries link physiology to inflammation
- 1Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
- 2Center for Global Non-Communicable Disease Research and Training, Johns Hopkins University, Baltimore, MD, USA
- Peter Jackson, Johns Hopkins University School of Medicine, Pulmonary Critical Care, 1830 E. Monument, 5th Floor, Baltimore, MD 21205-2105, USA. E-mail: pjacks35{at}jh.edu
Abstract
Does the high rate and unique risk factors of preserved ratio impaired spirometry in low- and middle-income countries have something to teach us about the physiology of this highly prevalent pattern? http://bit.ly/2SsQjeG
To the Editor:
We read with great interest the article by Wijnant et al. [1] in a recent issue of European Respiratory Journal investigating the longitudinal outcomes of patients with preserved ratio impaired spirometry (PRISm) in the Rotterdam cohort. PRISm is a subject of increased investigation as it is associated with respiratory symptoms, cardiovascular disease, metabolic syndrome and, quite clearly in the recent study, increased mortality [1–3]. While there have been numerous studies examining outcomes related to PRISm in high-income countries (HICs), few studies have assessed the clinical significance of this spirometric finding in low- and middle-income countries (LMICs).
Globally, 85% of non-communicable disease deaths occur in LMICs. Of these, chronic respiratory disease is the fourth leading cause of death and the World Health Organization predicted the largest increase in global mortality to be attributed to these disorders [4]. As the prevalence of chronic respiratory disease in LMICs is increasing, it is clear that PRISm is one of the most common spirometry findings in LMICs [5, 6]. Impairment on spirometry has been demonstrated to be as high as 60% among individuals with preserved forced expiratory volume in 1 s (FEV1)/forced expiratory volume (FVC) in the BOLD study and a more recent cross-sectional study in Malawi revealed 38.6% of participants with PRISm [6]. Furthermore, there are unique risk factors that may lead to the development of this spirometric pattern in LMICs. Wijnant et al. [1] found that incident PRISm was significantly higher in patients with elevated body mass index (BMI) (p<0.001 and p<0.010 respectively); this finding was also present in the COPDGene cohort [1, 3]. While obesity explains PRISm physiologically, its association with PRISm is not consistent. In the aforementioned Malawian and BOLD cohort, PRISm was paradoxically associated with lower BMI as well as poverty [5, 6]. There have been even fewer longitudinal studies of PRISm in LMICs. One, a study in urban and rural Peru demonstrated increased lung function decline (FEV1) among those with PRISm compared to normal spirometry [7], similar to the findings of Wijnant et al. [1]. It is worth noting, that high rates of PRISm could result from poorly performed spirometry, however, the studies mentioned conducted extensive training and ensured quality control checks on all spirometry data [5, 6, 8].
How can we reconcile the very high rates of PRISM in LMICs if not associated with extra-thoracic restriction? One hypothesis of interest is predicated on the association of PRISm with ambient pollution and organic inhalational exposures. The rates of PRISM are higher in smokers, as noted in the COPDGene and MESA studies [3, 8]. In LMICs, the rate of smoking remains much lower than that in HICs. However, biomass exposure and farming, which are prevalent through rural areas globally, have been strongly associated with impairment on spirometry in these settings. Additionally, the link between pollution and PRISm has been supported in numerous large cohorts in the USA and Europe [2]. Animal models further support this association, with links clearly identified between inhalational exposure, inflammation and impaired FVC [9]. All of these risk factors are far more prevalent in LMICs and may suggest a clue to the high prevalence in these settings.
So, what could be the common thread between the metabolic syndrome and inhalational exposure? A compelling association, described by Wijnant et al. [1] and demonstrated in LMIC settings, is systemic inflammation. In Peru, individuals with PRISm were more likely to have glucose intolerance and have elevated high-sensitivity C-reactive protein independent of obesity and other comorbidities, indicating that a similar inflammatory pattern found in high-income settings may be at play [8]. While diabetes has been associated with PRISm in HICs, there is evidence that impairment on spirometry precedes glucose intolerance. In the CARDIA study, individuals with higher fibrinogen experienced accelerated loss of lung function over time, though with a preserved ratio and a Swedish study reported similar findings with a range of circulatory inflammatory biomarkers [10, 11].
While compelling, the link between systemic inflammation and PRISm requires additional study. This will involve a commitment to establishing cohorts of PRISm patients in LMICs and ensuring that these patients obtain laboratory, radiological and detailed exposure assessments. In an ongoing project, our group at Johns Hopkins intend to evaluate PRISm patients from a large existing cohort in Kampala, Uganda with advanced pulmonary function testing and computed tomography scans. This study will allow comparisons of inhalational risk factors associated with this pattern and give additional longitudinal information about a LMIC cohort with high prevalence of PRISm.
Why does this matter in LMIC settings? With such a high prevalence of PRISm and clear evidence of increased mortality among patients with this physiological pattern, there may be a “time bomb” of patients that have thus far been overlooked. The increasing prevalence of spirometry in LMICs allows for increased recognition of this problem and the possibility for early intervention. All of these factors compel us to pursue further study of the PRISm phenotype, its associated risk factors and work to bridge the gap between PRISm patients in HICs and abroad.
Shareable PDF
Supplementary Material
This one-page PDF can be shared freely online.
Shareable PDF ERJ-00184-2020.Shareable
Footnotes
Support statement: This work was funded by the Fogarty International Center (grant: 5108724). Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: P. Jackson has nothing to disclose.
Conflict of interest: T. Siddharthan has nothing to disclose.
- Received January 28, 2020.
- Accepted January 30, 2020.
- Copyright ©ERS 2020