Ravi Kalhan, MD, MS: Defining Intermediary Respiratory Phenotypes

Published on: 

Strategic Alliance Partnership | <b>American Lung Association</b>

On the latest Lungcast, Kalhan reviewed a 2018 paper he and colleagues penned on the need to establish phenotypes of chronic lung disease progression—such as what cardiology has done with LDL-C for heart attacks.

A proposed reconceptualization of lifelong respiratory health modeling, originally published in 2018, could help provide pulmonologists what their peers in cardiology and other chronic disease-management spaces benefit from in long-term care: phenotypes for trajectory of lung health.1

In the March 2023 episode of Lungcast,2 Ravi Kalhan, MD, MS, deputy division chief of pulmonary and critical care medicine at the Northwestern Feinberg School of Medicine, discussed with Albert Rizzo, MD, chief medical officer of the American Lung Association (ALA), his research team’s work on developing a new respiratory health concept that projects individuals’ lung function decline over a lifetime—a deviation from the standard utility of pulmonary function testing.

“This concept of impaired respiratory health is predicated on the notion that you and I and every other lung doctor from time and eternity has defined disease by physiologic impairment,” Kalhan said. “We have always used pulmonary function as our key definition of COPD, for example, whereby if someone crosses a threshold of abnormal lung function…then you have obstructive lung physiology and you have COPD.”

In the case of this patient, their COPD may have been defined by a FEV1/FVC ratio of <70%, identified at age 57. The issue, Kalhan argues, is that pulmonologists are dispositioned to behave as if their lung function was normal at ages 40 and 50 prior to the COPD diagnosis. “But of course they were not normal,” he explained.

“They didn’t wake up one morning and develop chronic lung disease,” he continued. “It went through a progression across their life force, and by ignoring what we termed the ‘intermediate phenotypes’ of what someone looks as they transition from ideal respiratory health to chronic lung disease, we eliminate the opportunity to intercept the process and actually change the public health.”

Kalhan explained how pulmonology should look to emulate the phenotypes and biomarkers by which cardiovascular experts are able to intercept chronic disease progression risk in their own patients, such as LDL-C and its association with myocardial infarction risk.

“Those intermediate phenotypes inform disease interception and health promotion such that the burden of heart attacks go down in society,” Kalhan said. “And we need think creatively in the respiratory space about how to do that, and that’s the fundamental thought behind the framework we presented in that paper.”

Lungcast is a monthly respiratory health podcast series from the ALA produced by HCPLive.

Subscribe or listen to Lungcast on Spotify here.


  1. Reyfman PA, Washko GR, Dransfield MT, Spira A, Han MK, Kalhan R. Defining Impaired Respiratory Health. A Paradigm Shift for Pulmonary Medicine. Am J Respir Crit Care Med. 2018;198(4):440-446. doi:10.1164/rccm.201801-0120PP
  2. Kunzmann K. The Future of Lung Disease Interception with Ravi Kalhan, MD, MS. HCPLive. Published March 14, 2023. Accessed April 11, 2023.