nonspecific pattern and PRISM in PFT


  • nonspecific: reduced FEV1 or FVC and normal FEV/FVC ratio and normal TLC
    • reduced effort: not breathing all the way out. (flow volume curve concave towards end?)
    • early restriction: FVC smaller but RV the same
    • early obstruction: small airway disease, FVC smaller and RV increased. FEV/FVC has not started to fall yet.
  • PRISM: preserved ratio impaired spirometry. This is when the TLC is not measured1

Large population-based studies have demonstrated that symptomatic current or former smokers with a proportionate decrease in FEV1 and FVC resulting in a preserved FEV1/FVC ratio have greater respiratory symptoms, reduced exercise capacity, and increased all-cause mortality compared with smokers with normal lung function (choice D is correct). This patient has preserved ratio impaired spirometry (PRISm). Alternative names in the literature have previously included nonspecific, restrictive subtype or Global Initiative for Obstructive Lung Disease (GOLD)-unclassified spirometric pattern.

The prevalence of PRISm ranges from 5% to 20% (choice A is incorrect). In the COPDGene study, the prevalence was 12%. Longitudinal studies of smokers with at least a 10-pack-year smoking history and without airflow obstruction on spirometry have demonstrated that many have respiratory symptoms such as cough, sputum production, and shortness of breath suggestive of COPD, with exacerbations and activity limitation. Despite a lack of flow limitation on spirometry, a significant number of smokers have evidence of structural lung disease based on the presence of emphysema, airway wall thickening, and air trapping. Diffusing capacity measurements and CT imaging are not commonly reported in PRISm studies to speculate about the incidence of underlying structural lung disease.

PRISm is not uniformly progressive, with only 15% to 25% of those with PRISm and total lung capacity greater than the lower limit of normal (LLN) developing obstructive spirometry over time (median follow-up of 3 years). Studies, however, have shown significant heterogeneity, with some individuals progressing to classic airflow obstruction, with others normalizing their lung function; about half transition to and from PRISm. Longitudinal data suggest that individuals who transition between PRISm and classically obstructed states have increased mortality. While there are some transitions in lung function due to the “noise” of spirometric testing, the significant number of individuals with PRISm who transition between categories have led some to conclude that there is greater spirometric variability for these individuals. Nonetheless, GOLD advocates for repeated measurements on separate occasions of the postbronchodilator FEV1/FVC ratio for those who straddle cutoff thresholds.

No single genetic variant has been identified as being associated with PRISm. Interestingly, however, an association with Klinefelter syndrome has been observed.

There is a lack of consensus about whether a fixed cutoff (GOLD) or LLN cutoff (defined as lower than the fifth percentile of a healthy reference group adjusted for age, sex, race, and height) should be used in defining PRISm. Both thresholds are used to define a COPD population, each with advantages and disadvantages, though a large pooled data study of >20,000 adults demonstrated that a fixed cutoff was more accurate than the LLN in identifying patients who experienced COPD-related events. However, since FEV1 is primarily a measure of airflow in central airways, and COPD is mainly a disease of the small airways, the FEV1/FVC ratio may be an insensitive measure of early disease. Studies of PRISm are limited, though they suggest that clinical and radiographic data should be incorporated into physiological data when diagnosing COPD.

Footnotes

  1. ERS ATS technical standard on interpretive strategies for routine lung function tests