Higher BMI associated with favorable clinical outcomes in patients with cystic fibrosis
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In a systematic review and meta-analysis, researchers found higher BMI was associated with favorable clinical outcomes in patients with cystic fibrosis, urging reconsideration of the currently recommended target BMI.
“Currently, BMI is the generally accepted indicator for monitoring the nutritional status of patients with cystic fibrosis. In children older than 2 years, the target BMI is at least the 50th percentile; in adults, the target BMI is greater than or equal to 22 for women and greater than or equal to 23 for men,” Rita Nagy, MD, from the Institute for Translational Medicine at Szentágothai Research Centre Medical School at the University of Pécs, the Centre for Translational Medicine at Semmelweis University and the Heim Pál National Pediatric Institute, Budapest, Hungary, and colleagues wrote in JAMA Network Open. “However, BMI does not distinguish between the major components of the body, namely, fat mass, fat-free mass, total body water, bone mineral density and bone mineral content.”
Researchers conducted a literature search of the MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases in November 2020. Their search identified 17 studies that enrolled 9,114 patients aged 2 years and older with cystic fibrosis with altered BMI or body composition who were compared with patients with measured parameters in the reference ranges.
The primary outcomes were pulmonary function, exocrine pancreatic insufficiency and cystic fibrosis-related diabetes.
Compared with those with normal weight, researchers observed higher FEV1 among those who were overweight (–8.36%; 95% CI, –12.74 to –3.97) and obese (–12.06%; 95% CI, –23.91 to –0.22).
In addition, likelihood for cystic fibrosis-related diabetes and pancreatic insufficiency was higher among patients with normal weight (OR = 1.49; 95% CI, 1.1-2) compared with those with overweight (OR = 4.4; 95% CI, 3-6.45).
Researchers found high heterogeneity in the analysis of pulmonary function with a heterogeneity statistic I2 of 46.7% to 85.9%.
“Our findings suggest that nutritional status plays an important role in maintaining organ function in patients with cystic fibrosis. Because we noted that a higher BMI is associated with better clinical parameters, we advise clinicians to reconsider increasing the currently recommended target BMI. The use of a nutritional strategy that increases BMI, at least until the upper limit of normal BMI is reached, should be included in the daily protocol. Our results suggest that careful evaluation of body composition should be incorporated into everyday clinical practice,” the researchers wrote.
In an accompanying editorial, Christina S. Thornton, MD, PhD, postdoctoral research fellow at the University of Michigan Ann Arbor, said the association between improved lung function and higher BMI in this study “warrants careful consideration toward optimal targets of BMI” in patients with cystic fibrosis.
“Obesity is a major global health concern and is associated with increased morbidity and mortality due to higher rates of heart disease, hypertension and diabetes. Thus, emerging concern over patients with cystic fibrosis who are overweight or obese experiencing these detrimental health conditions is justified, particularly in the era of modulator therapies. ... Further longitudinal studies to address the consequences associated with overweight status in patients with [cystic fibrosis] to optimize nutritional approaches and treatment plans will be required to help guide further clinical recommendations,” Thornton wrote.
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The systematic review and meta-analysis performed by Nagy and colleagues is a robust study with interesting findings. They analyzed a large pooled cohort of individuals with cystic fibrosis, and analyzed the association between BMI and clinical outcomes (lung function, pancreatic insufficiency and cystic fibrosis-related diabetes). The authors found that higher BMI, including overweight and obese categories, were associated with higher lung function and lower rates of pancreatic insufficiency and cystic fibrosis-related diabetes. Current cystic fibrosis guidelines recommend individuals with cystic fibrosis have a normal BMI, but the authors recommended that clinicians reconsider increasing this recommended target BMI.
While this study was done rigorously, I think caution is needed before changing BMI recommendations. Higher BMI in the overweight and obese categories are well known to be associated with higher morbidity and mortality due to cardiovascular disease (hypertension, stroke, heart attacks, diabetes) in the general population. Historically, individuals with cystic fibrosis have had a lower survival rate than the general population (individuals born with cystic fibrosis in the 1950s might not live past 5 years old; in the 1970s, mid-teens.) With the improvement in medications targeting infection as well as the underlying defect in cystic fibrosis, individuals with cystic fibrosis born between 2015 and 2019 have an average survival of 46 years old. Great news is that survival is improving in cystic fibrosis. However, not many individuals with cystic fibrosis have developed CVD given the shortened survival, yet we expect survival in individuals with cystic fibrosis to continue to increase over the next decade.
Therefore, many individuals with cystic fibrosis will come of age when CV complications may develop, and we will need further long-term studies to accurately assess the potential complications associated with a higher-than-normal BMI in individuals with cystic fibrosis. Furthermore, many individuals who are eligible for CFTR modulators — medications that correct the underlying defect in cystic fibrosis — have had large increases in their lung function to normal or near-normal levels, and it would be those individuals who would not benefit from any “extra” lung function that might be associated with a higher BMI. In fact, the risk of CV complications would not outweigh the lung function benefit they might receive.
A limitation that the authors did not discuss is that the studies included in the meta-analysis were all conducted before Trikafta was approved in the U.S. (October 2019), which approximately 90% of people with cystic fibrosis are eligible for. Trikafta is associated with an average of 10% to 15% improvement in lung function and a drastic improvement in many other clinical outcomes. Some of our patients have seen their lung function improve by even 20% to 30%. Rates of hospitalizations are decreasing. Given the benefit we are seeing with Trikafta and other highly effective modulators, the lung function benefit associated with being overweight or obese may not be needed. For those individuals not eligible for modulators currently, there could be a benefit for a higher BMI in order to attain a higher lung function. However, that would need to be balanced by the risk of cardiovascular complications and considered on an individual patient basis.
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