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Low BMI, Weight Loss Predict Mortality Risk in ILD

A low body mass index (BMI) indicative of being underweight as well as a weight loss of 2 kg or more over the course of 1 year were both independently associated with a higher mortality risk in the following year in patients with fibrotic interstitial lung disease (ILD). In contrast, being both overweight and obese appeared to be protective against mortality at the same 1-year endpoint, according to the results of an observational, retrospective cohort study.

Compared to patients with a normal BMI, patients who were underweight at a BMI of <18.5 kg/m2 were over three times more likely to die at 1 year, at a hazard ratio (HR) of 3.19 (P < .001), senior author Christopher Ryerson, MD, University of British Columbia, Vancouver, and colleagues report in the journal Chest.

In contrast, patients who were overweight with a BMI of 25 to 29 kg/m2 had roughly half the mortality risk as those who were underweight, at an HR of 0.52 (P < .001). Results were roughly similar among the patients with obesity with a BMI in excess of 30 kg/m2, among whom the HR for mortality at 1 year was 0.55 (P < .001) compared to those who were underweight.

“All patients with fibrotic ILD should still engage in exercise and eat an appropriate diet and it is still OK if you are obese and lose weight as a consequence of these lifestyle choices,” Ryerson told Medscape Medical News in an email.

“But physicians should be concerned about patients who have severe ILD and who start to lose weight unintentionally since this often represents end-stage fibrosis or some other major comorbidity such as cancer,” he emphasized.

Two Large Cohorts

Patients from two large cohorts, including the six-center Canadian Registry for Pulmonary Fibrosis (CARE-PF) and the ILD registry at the University of California, San Francisco (UCSF), were enrolled in the study. A total of 1786 patients were included from the CARE-PF registry, which served as the derivation cohort, while another 1779 patients from the UCSF registry served as the validation cohort. In the CARE-PF cohort, 21% of all ILD patients experienced a weight loss of at least 1 kg in the first year of follow-up, including 31% of patients with idiopathic pulmonary fibrosis (IPF).

“Fewer patients experienced a weight loss of at least 1 kg during the first year of the study period in the UCSF cohort,” the authors note, at only 12% of all ILD patients, some 14% of those with IPF losing at least 1 kg of weight over the course of the year. At 2 years’ follow-up, 35% of all ILD patients had lost at least 1 kg, as had 46% of all IPF patients. Looking at BMI, “a higher value was associated with decreased 1-year mortality in both cohorts on unadjusted analysis,” the investigators observe.

In the CARE-PF cohort, the HR for 1-year mortality was 0.96 per unit difference in BMI (P < .001), while in the UCSF cohort, the HR for 1-year mortality was exactly the same, at 0.96 per unit difference in BMI (P < .001). The authors then adjusted findings for the ILD-GAP index, which included gender, age, and physiology index. After adjusting for this index, the HR for 1-year mortality in the CARE-PF cohort was 0.93 per unit change in BMI (95% CI, 0.90 – 0.967; P < .001), while in the UCSF cohort, the HR was 0.96 per unit change in BMI (95% CI, 0.94 – 0.98; P = .001).

Indeed, each 1-kg change above a BMI of 30 kg/m2, adjusted for the ILD-GAP index, was associated with a reduced risk of mortality at 1 year in both cohorts, at an HR of 0.98 (P = .001) in the CARE-PF cohort and an HR of 0.98 (P < .001) in the UCSF cohort. In contrast, patients who experienced a BMI weight loss of 2 kg or more within 1 year had a 41% increased risk of death in the subsequent year after adjusting for the ILD-GAP index and baseline BMI category, at an HR of 1.41 (P = .04). “The absolute change in mortality is much smaller than this,” Ryerson acknowledged.

“However, the magnitude [in mortality risk] did impress us and this illustrates how weight loss is a frequent consequence of end-stage disease which is something that we have all observed clinically as well,” he added. Mortality risk plateaued in patients with a greater weight loss, investigators observe, and there was no association between weight and subsequent 1-year mortality in either cohort on unadjusted analysis.

On the other hand, being underweight was associated with between a 13% and 16% higher mortality risk at 1 year after adjusting for the ILD-GAP, at an HR of 0.84 per 10 kg (P = .001) in the CARE-PF cohort and an HR of 0.87 per 10 kg (P < .001) in the UCSF cohort. “Results were similar in the two studied cohorts, suggesting a robust and generalizable association of both low BMI and weight loss with mortality,” the authors emphasize.

“Together these studies highlight the potential link between obesity and ILD pathogenesis and further suggest the possibility that nutritional support may have a more specific and important role in the management of fibrotic ILD,” the authors emphasize. Ryerson in turn noted that being able to determine mortality risk more accurately than current mortality risk prediction models are able to do is very helpful when dealing with what are sometimes life and death decisions.

He also noted that having more insight into a patient’s prognosis can change how physicians manage patients with respect to either transplantation or palliation and potentially the need to be more aggressive with pharmacotherapy as well.

Addressing Weight Loss

Asked to comment on the findings, Elizabeth Volkmann, MD, associate professor of medicine, University of California, Los Angeles, said that this was a very important study and something that she feels does not get adequate attention in clinical practice.

“Weight loss and malnutrition occur in many patients with ILD due to various factors such as gastrointestinal side effects from anti-fibrotic therapies, decreased oral intake due to psychosocial issues including depression, and increased caloric requirements due to increased work of breathing,” she observed in an email to Medscape Medical News. That said, weight loss and malnutrition are still often underaddressed during clinical encounters for patients with ILD where the focus is on lung health.

“This study illuminates the importance of addressing weight loss in all patients with ILD as it can contribute to heightened risk of mortality,” Volkmann reemphasized. Volkmann and colleagues themselves recently reported that radiographic progression of scleroderma lung disease over the course of 1 to 2 years is associated with an increased risk of long-term mortality, based on two independent studies of systemic sclerosis-interstitial lung disease (SSc-ILD) with extensive follow-up.

Over 8 years of follow-up, patients in the Scleroderma Lung Study II (SLS II) who exhibited an increase of 2% or more in the QILD score — a score that reflects the sum of all abnormally classified scores, including those for fibrosis, ground glass opacity, and honeycombing — for the whole lung at 24 months had an almost fourfold increased risk in mortality, which was significant (P = .014).

The association of an increase in the QILD ≥2% at 12 months was suggestive in its association with mortality in the SLS I cohort at 12 years of follow-up, a finding that suggests that radiographic progression measured at 2 years is a better predictor of long-term mortality than at 1 year, as the authors concluded.

The CARR-PF is funded by Boehringer Ingelheim. Ryerson reports receiving personal fees from Boehringer Ingelheim. Volkmann consults or has received speaker fees from Boehringer Ingelheim and has received grant support from Kadmon and Horizon Therapeutics.

Chest. Published online November 14, 2021. Abstract

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