PRIsm – Diagnosis and approach

Background of PRISm
Chronic obstructive pulmonary disease (COPD) is prevalent among an elderly and is a significantly associated to global morbidities and mortality. Furthermore, the impaired lung growth can lead to COPD and has been purposed as the pathogenesis in the absence of a rapid decline in lung function from aging. Hence and preserved ratio impaired spirometry (PRISm) has been proposed as a concept of COPD subtype or early COPD. Despite that poor lung function and smoking are risks for the PRISm, obesity and restrictive lung disease are also associated with PRISm. 

Definition 
Preserved ratio impaired spirometry (PRISm) is a spirometric pattern associated with significant respiratory symptoms and increased mortality. Individuals with PRISm represent a heterogenous group of lung diseases. PRISm was defined as the ratio of FEV1/FVC > lower limit of normal and FEV1 < lower limit of normal using reference values. Hence, PRISm is defined by a forced expiratory volume in one second (FEV1) that is less than 80% of the predicted value, whilst maintaining a FEV1/FVC ratio > 0.7 PRISm represents a state of diminished lung function in epidemiological studies. 

PRISm and COPD
According to the Global Initiative for Obstructive Lung Disease (GOLD), COPD is diagnosed by the post-bronchodilator FEV1/FVC ratio < 0.7. However, PRISm represents a distinct spirometric parameters from COPD. It is characterized by a proportional decline in both FEV1 and FVC, with maintaining the normal range of FEV1/FVC ratio. It is formerly recognized as GOLD unclassified or restrictive lung function. Despite the absence of spirometric criteria of airflow obstruction in PRISm, the higher risk of progressing to COPD was noted smokers with PRISm compared to smokers with normal lung functions. To date, it remains controversial whether the PRISm affects the development of COPD. Collectively, PRISm has been identified as a COPD subtype that is susceptible to progression of COPD. Epidemiological study has reported that one-third of individuals with PRISm progressed to COPD within 5 years. In addition, PRISm increased experiencing COPD exacerbations despite of very stable clinical course. 

The diagnosis of PRISm and prevalence 
The PRISm is physiologically defined as abnormal non-obstructed spirometry, or restrictive spirometry. It occurs in 7–12% of the general population. Moreover, the definition and diagnosis of PRISm are overlapped with other respiratory diseases. Since it relies on the spirometric parameters of FEV1/FVC ratio and the predicted FEV1. Individuals with PRISm represent a heterogenous population that is associated with obesity, and other restrictive lung disease such as interstitial lung diseases. To clearly identify PRISm in clinical arena remains dilemma for clinicians these days. Meanwhile, the PRISm is perceived as a transitional state to COPD. Lastly it is prone to developing COPD and increased risk of exacerbations.

Pathology and pathophysiology
Epidemiological study did not identify direct genetic variants associated with PRISm. Moreover, tobacco smoking is an important etiological factor for PRISm and COPD. Since the proportion of patients with PRISm have a history of tobacco smoking as COPD patients. The higher numbers of current smokers and a higher average pack-year of smoking was observed in the PRISm. The body mass index (BMI) is crucial factor for PRISm. One way, the obesity leads to mechanical compression of lungs as well as local and systemic inflammation. While, the underweight increases the risk of PRISm as a results of reduced respiratory muscle strength, impaired lung development, and the increased risk of infections.

Lung imaging in PRISm 
Since computed tomography (CT) of chest is more sensitive than pulmonary function tests such as spirometry for the detection of early-stage COPD. The parenchymal destruction, airways and pulmonary vasculature vascular changes has been demonstrated in The PRISm. The mean lung density (MLD) is highly variable variations among COPD and PRISm. The MLD of the early-stage COPD was significantly reduced in comparison to the PRISm. The pulmonary emphysema in PRISM is an independent predictor for COPD.  The percentage of airway wall (AW) area in CT is also the independent prognosis for PRISm.  

Prevention and Treatments of PRISm 
To date, there remain no definitive and well-established recommendation for diagnosis, evaluation and management for the PRISm. Treatment for PRISm may include anti-inflammatory drugs, bronchodilator therapies, pulmonary rehabilitation and appropriate nutritional support for both airway-predominant type and emphysema-predominant type of COPD. Moreover, there is a lack of randomized control trial examining and confirming the therapeutic effects biologics in the treatment of PRISm. Future therapeutic paradigm and management strategies should be investigated for the potential clinical application for PRISm. Ultimately, tobacco smoking cessation has been shown the benefit with PRISm prognosis as it is able to reduce the risk of mortality and the delayed progression of airflow limitation. 

References 
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10. Kawamatawong T, Rungsrisasithorn N, Wudhikulprapan W, Sukkasem W.Prevalence of Chronic Obstructive Pulmonary Disease with Preserved Ratio Impaired Spirometry (COPD-PRISM) and Clinical Outcomes in Tertiary Care Setting Thailand. Am J Respir Crit Care Med. 2019;199: A1596. https://doi.org/10.1164/ajrccm-conference.2019.199.1_Meeting Abstracts.A1596